Deals Shaping The Medical Industry, May 2015

Derived from Strategic Transactions, Informa’s premium source for tracking life sciences deal activity, the Dealmaking column is a survey of recent health care transactions listed by relevant industry segment – In Vitro Diagnostics, Medical Devices, Research/Analytical, and Pharmaceuticals – and then categorized by type – Acquisition, Alliance, or Financing. This month’s column covers deals announced April 2015.

IN VITRO DIAGNOSTICS

Mergers & Acquisitions

Rosetta Genomics Ltd.

Prelude Corp.

PersonalizeDx

Rosetta Genomics Ltd. paid $2mm in cash and $1.5mm in stock (500k shares) to acquire private diagnostics company CynoGen Inc. (also known as PersonalizeDx) from Prelude Corp. As a form of payment, Rosetta will also provide Prelude with some assets and services. (Apr.)

Prelude is in the process of closing its acquisition of PersonalizeDx from Abbott Molecular. PersonalizeDx's molecular diagnostics use fluorescence in situ hybridization (FISH) to detect genomic changes in prostate, bladder, breast, and lung cancers. Through its CLIA lab, PersonalizeDx offers laboratory testing services including companion diagnostics, one of which is Abbott's Vysis ALK, used with Pfizer's Xalkori (now being co-promoted with Merck KGAA). In 2014, PersonalizeDx's unaudited revenue totaled $6.9mm. The company's products will complement Rosetta's microRNA biomarker tests for cancer origin, lung cancer, kidney cancer, and mesothelioma. In addition, Rosetta hopes the addition of PersonalizeDx will aid in the launch of its thyroid neoplasia assay later this year. Concurrent with the PersonalizeDx acquisition, Rosetta also received rights to Prelude's multi-marker assay that assesses the risk for cancer recurrence in ductal carcinoma in situ.

Alliances

Abbott Laboratories Inc.

Sekisui Medical Co. Ltd.

Sekisui Medical Co. Ltd. licensed Abbott Laboratories Inc. exclusive rights to distribute its CP3000 coagulation test in the US, Europe, and other areas that grant the CE mark. Abbott also receives non-exclusive distribution rights in China, Hong Kong, Japan, and Macau. (Apr.)

Expanding its hematology portfolio, Abbott should begin selling the product in Europe later this year and in the other regions in 2016. The CP3000 automated coagulation analyzer incorporates high-quality reagents and a broad assay menu to provide rapid results. Such coagulation tests can help physicians assess a patient’s risk for excessive bleeding or developing clots. The system will work with Abbott's Acceleratora3600 lab automation platform and middleware solutions.

Prelude Corp.

Rosetta Genomics Ltd.

Prelude Corp. licensed Rosetta Genomics Ltd. rights to sells its assay for ductal carcinoma in situ (DCIS), a noninvasive type of breast cancer. (Apr.)

Using funds from two SBI grants (together worth $927k), Prelude has developed a multi-marker test that can help determine which patients would be likely to encounter cancer recurrence and require post-surgery radiation following DCIS diagnosis. Prelude is a University of California, San Francisco spin-off and is backed by Fjord Ventures. Concurrent with the alliance, Prelude sold CynoGen Inc. (doing business as PersonalizeDx) to Rosetta for $3.5mm in cash and stock.

Financings

Biocartis NV

Belgian diagnostics company Biocartis NV grossed €100mm ($107mm) in its initial public offering on Euronext Brussels, selling 8.7mm shares for €11.50, the high end of its €10-11.50 range. Belgian retail and institutional investors participated. (Apr.)

Investment Banks/Advisors: KBC Securities; Kempen & Co.; Petercam Group

Trinity Biotech PLC

Trinity Biotech PLC (diagnostics for infectious, autoimmune, and metabolic diseases) netted $110.9mm (including the full exercise of the overallotment) through the sale of 4% exchangeable unsecured senior notes due 2045. The interest on the notes will be paid semi-annually in arrears on each April 1 and October 1 beginning October 1, 2015 and are not redeemable until after April 1, 2020. The exchange rate will equal 45.1488 ADSs per $1k principal of notes, equaling an initial exchange price of $22.15 per ADS (15% premium). The proceeds will be used to fund future acquisitions and continued product development and commercialization. (Apr.)

MEDICAL DEVICES

Mergers & Acquisitions

Boston Scientific Corp.

XLumena Inc.

Boston Scientific Corp. is acquiring private diagnostic imaging device maker Xlumena Inc. for $62.5mm up front, $12.5mm upon FDA approval of the next-generation Hot Axios system, and additional sales milestones through 2018. (Apr.)

Founded in 2007, Xlumena is developing minimally invasive devices that use endoscopic ultrasound to allow gastroenterologists to view organs around the GI tract. Its FDA-approved and CE-marked Axios system was the first available stent to provide endoscopic ultrasound-guided (EUS) transluminal drainage of symptomatic pancreatic pseudocysts. The follow-on product, Hot Axios, incorporates cautery into the delivery of the Axios stent; it is already cleared in Europe, where it is sold in various countries. These products will complement Boston Scientific’s EUS portfolio of minimally-invasive treatments for pancreatic pseudocysts, including Expect endoscopic ultrasound aspiration needles. Xlumena raised $38mm in its first three financing rounds; investors include Third Point, Prism VentureWorks, Charter Life Sciences, Ascent Biomedical Ventures, and Aperture Venture Partners. Just last month Boston Scientific paid $1.6bn in cash plus potential earn-outs for the men’s health business of Endo International’s American Medical Systems.

Spinal Modulation Inc.

St. Jude Medical Inc.

St. Jude Medical Inc. exercised its exclusive option to buy Spinal Modulation Inc. and will pay $175mm, plus earn-outs upon FDA approval of the Axium intraspinal neurostimulator system and achievement of certain revenue goals. (Apr.)

St. Jude received the option in June 2013 when it made a $40mm equity investment in Spinal Modulation and got an exclusive option to distribute Axium in international markets where it is approved. (The device gained the CE mark in November 2011 for managing chronic pain.) Spinal Modulation was already granted IDE exemption and recently submitted the PMA application to the FDA. Axium uses spinal cord stimulation (SCS) to target the dorsal root ganglion (DRG), which contains nerve fibers that carry signals to the brain. This type of therapy offers a new option for managing pain, including chronic intractable leg pain and in difficult areas to target such as the back and foot. Traditional SCS targets nerves along the dorsal column of the spinal cord, an approach in which it’s often difficult to isolate the exact painful area. Post-transaction, St. Jude is the only medical device company with products for radiofrequency ablation, SCS, and DRG.

Alliances

Biomet Inc.

Limacorporate SPA

Zimmer Holdings Inc.

Limacorporate SPA is buying Zimmer Biomet Holdings Inc.’s Zimmer Unicompartmental High Flex Knee (ZUK) and Biomet Inc.’s Discovery elbow system within the European Economic Area (EEA) and Switzerland markets, and Biomet’s Vanguard complete knee system for Denmark and Sweden. (Apr.)

Last year Zimmer agreed to buy Biomet for $10.35bn in cash and $3bn in Zimmer stock. In March 2015, that deal was approved by EU antitrust authorities on the condition that three businesses, which are now being purchased by Lima, be divested to improve competitiveness across the EEA. Lima also gets a nonexclusive EEA-wide license relating to the manufacturing, marketing, and sales of an exact copy of the Vanguard knee. With ZUK, Lima now has a presence in the unicompartmental knee segment. The company will launch its own Physica total knee in a few days. Lima is a leading playing in the shoulder market with its arthroplasty implant. Now having Discovery in its portfolio, the company can strengthen its extremities business. The current agreement with Lima becomes effective once the Zimmer/Biomet acquisition officially closes.

Dalton Medical BV

Viveve Medical Inc.

Viveve Medical Inc. granted Dalton Medical BV rights to sell the Viveve vaginal laxity system in the Netherlands, Belgium, and Luxembourg. (Apr.)

Viveve is a nonsurgical, nonablative device that uses radiofrequency energy to stimulate the collagen rebuilding process to treat vaginal laxity, a common condition caused by childbirth that results in loss of vaginal tightness as well as a decrease in physical sensation and sexual satisfaction. The system is approved for sale in Europe, Canada, Hong Kong, and Japan (in certain circumstances). Dalton is the third company signed on to market Viveve in recent months. Global DIA Solutions will sell it in Spain, while CoachHouse Medical has rights in the UK.

DreaMed Diabetes

Medtronic PLC

In its first alliance, DreaMed Diabetes licensed Medtronic PLC exclusive worldwide rights to develop and market products that incorporate the MD-Logic artificial pancreas algorithm. (Apr.)

Medtronic will pay DreaMed sales royalties on any resulting products and also made a $2mm equity investment in the start-up. Medtronic will use DreaMed’s MD-Logic in its own insulin pumps and glucose monitoring system. DreaMed has incorporated MD-Logic into its lead product GlucoSitter, which is a fully automated, closed-loop artificial pancreas system for controlling glucose levels. The software continuously monitors glucose levels and can precisely adjust insulin levels as needed. Medtronic hopes to create a device that can help minimize the risk of low and high blood glucose episodes, and allow diabetics to better manage their disease.

EarlySense Ltd.

Mitsui & Co. Ltd.

In its first major partnership, EarlySense Ltd. licensed Mitsui & Co. Ltd. exclusive Japanese rights to its patient monitoring and at-home wellness/sleep improvement devices. (Apr.)

Concurrent with the alliance, EarlySense received $5mm from Mitsui in the second tranche of the company's Series F financing, which initiated in January 2015 and now totals $25mm (EarlySense has now raised about $63mm in venture equity to date). EarlySense's sensor, which is placed under the patient's mattress, detects mechanical vibrations of the heart cardio ballistic effect and respiratory and patient movement to continuously monitor these vital signs and transmit signals to a beside monitor. The data is then analyzed to measure heart and respiratory rates, and the information is sent to a central display station. The system can improve patient safety and provide health care professionals with early warnings of patient deterioration. The at-home wellness/sleep device is still under development in the US, Europe, and Asia. EarlySense, based in the US and Israel, has been expanding in Asia. In February the company's patient monitor received regulatory approval in South Korea.

Fresenius SE & Co. KGAA

Fresenius Medical Care AG

Sequana Medical AG

Sequana Medical AG licensed Fresenius Medical Care AG rights to distribute in Europe, the Middle East, and Africa its alfapump device for ascites removal. (Apr.)

Fresenius' initial efforts will be focused on Austria, Belgium, the Netherlands, and Poland, where the company will work on market development and reimbursement programs. Sequana, which has raised at least $52mm in equity to date, received CE mark approval for alfapump in 2011. The subcutaneous implant continuously removes ascites (excess fluid build-up) from the abdomen and transfers the ascites, via a catheter, to the bladder where they're passed naturally with urine. Sequana also has a new technology, called DirectLink, which allows remote observation of ascite removal. Patients suffering from severe liver damage and abdominal cancer, as well as those with pancreatitis, congestive heart failure, and portal vein thrombosis, can experience ascites, which are caused by high pressure in the blood vessels of the liver and by a lack of albumin. Alfapump is a much less invasive alternative to paracentesis procedures, which involve inserting a tube into the stomach to remove the fluid. Fresenius says alfapump will complement its liver support system Prometheus, an extracorporeal device that filters blood to separate toxins bound to albumin.

PHARMACEUTICALS

Mergers & Acquisitions

Celgene Corp.

Quanticel Pharmaceuticals Inc.

Three-and-a-half years after paying $45mm for an undisclosed stake in the company, Celgene Corp. has exercised its option to buy privately held Quanticel Pharmaceuticals Inc. outright for $100mm up front. The deal also includes up to $385mm in earn-outs based on R&D and regulatory progress. (Apr.)

Celgene now gets full control of Quanticel’s single-cell genomic analysis platform, which examines the behavior of individual cells during tumor growth to help determine those that may become resistant to certain drugs. During the option period, Quanticel used its technology to discover candidates that are expected to enter clinical trials early next year. The company was formed in 2010 by Stanford professors Dr. Stephen Quake and Dr. Michael Clarke, and in addition to the investment from Celgene, was backed by Versant Ventures. The acquisition of Quanticel wraps up a busy April for Celgene; it just paid $450mm up front for rights to develop MedImmune’s MEDI4736 (durvalumab) for blood cancers, and prior to that had purchased an 11% stake (worth $44mm) in regenerative medicine firm Mesoblast (and took a six-month right of first refusal to certain of Mesoblast’s mesenchymal lineage adult stem cell compounds).

Cipher Pharmaceuticals Inc.

Innocutis Holdings LLC

Cipher Pharmaceuticals Inc. paid $45.5mm up front for private dermatological drug and device developer Innocutis Holdings LLC, which could also receive up to $3mm over the next three years if financial performance targets are met. (Apr.)

To help fund the up-front payment, Cipher drew down $40mm out of $100mm in a notes offering from Athyrium Capital Management. Innocutis brings products that are complementary to Cipher, which is already active in dermatology. Cipher's portfolio includes Absorica for severe nodular acne (sold in the US by Ranbaxy), and the Beteflam patch (licensed from Institut Biochimique) for plaque psoriasis and eczema (available in Canada). In just 2015, Cipher has also acquired rights to dermatology products from Can-Fite and Astion Pharma, and bought Melanovus Oncology, which has candidates for melanoma and other skin cancers. But via Innocutis, Cipher will now have a direct US presence, including a 31-person sales force covering 3.5k dermatologists across 28 states. Conversely, Innocutis' drugs will get broader exposure in Canada. Innocutis, which was founded in 2005, has seven marketed prescription drugs. It co-promotes Bionect (hyaluronic acid) for skin irritation and first- and second-degree burns with DARA BioSciences in the US (DARA targets certain oncology markets, including post-radiation and post-chemotherapy skin erythema, desquamation, rash, itching, ulceration, and pain). Innocutis holds North American rights to Sitavig (acyclovir), launched in Q3 2014 for cold sores, from BioAlliance Pharma under 2014 deal. Innocutis is also involved in devices via its Insorb absorbable skin stapler, which is partnered with Incisive Surgical. Innocutis had $10.1mm in 2014 net product revenue. The company's only publicly disclosed financing was done in 2011 and totaled $6.5mm from Ballast Point Ventures.

Clinigen Group PLC

Idis Group Holdings Limited

Clinigen Group PLC acquired Idis Group Holdings Ltd. for $342mm (£225mm). The acquisition will be immediately earnings-enhancing and Clinigen expects to receive approximately $3.8mm in annual cost synergies. The transaction will be financed from a fully underwritten vendor placing and from new debt facilities. (Apr.)

Idis operates through two business divisions, a managed access division focused on providing access to clinical phase and pre-approved medicines via "managed access" programs, and a general access division which provides access to medicines already approved in another market. The two companies will create a market leader in the $5bn ethical unlicensed supply of medicines and strengthen their position in the $2bn clinical trial supply market. Investment Banks/Advisors: Numis Securities Ltd. (Clinigen Group PLC )

Karo Bio AB

Tanomed AB

Karo Bio AB is buying fellow Swedish biotech Tanomed AB for SEK20mm ($2.3mm) in stock (13.48mm shares at SEK1.48 each). (Apr.)

Karo Bio gains Tanomed’s drug that’s designed to prevent progression of the common cold by reinforcing the body’s own defenses to fight the virus. Based on technology from the University of Umea, the therapy combines the enzyme glucose oxidase with glucose to counteract rhinovirus infections and other viruses and bacteria. Clinical trials have demonstrated positive results thus far. A launch could come within a year-and-a-half.

Mylan NV

Perrigo Co. PLC

Mylan NV made an unsolicited offer to acquire public OTC and generic pharmaceuticals company Perrigo Co. PLC in a cash and stock transaction valued at $28.9bn. Perrigo shareholders would receive $205 in combined cash and Mylan stock representing a 24.2% premium. The Perrigo board is currently evaluating the unsolicited offer. The companies have had ongoing discussions over a potential combination over the past few years. If approved, this would be Mylan's largest M&A to date. (Apr.)

The combined entity would have $15.3bn in 2014 proforma sales (in the year ended June 28, 2014, Perrigo reported net sales of $4.1bn, $205mm net income, and $800mm in cash), highly complementary businesses with attractive portfolios across generics, specialty, and nutraceuticals, a powerful commercial platform, and strong R&D capabilities. The deal would also provide Mylan with an entry into the OTC market after its failed attempt to buy Meda last year. In January, Mylan got final approval to acquire Abbott Laboratories Inc.’s non-US developed markets specialty and generics businesses in a deal that changed its headquarters from Pittsburgh to the Netherlands, and on March 30 Perrigo closed its $4.5 billion acquisition of Omega Pharma NV. Investment Banks/Advisors: Goldman Sachs & Co. (Mylan NV)

April 2015 updates: The Perrigo board of Directors unanimously rejected the offer, concluding that the proposal substantially undervalues the company. On the same day, [Teva] made an unsolicited bid to acquire Mylan in a deal worth $40bn. Teva said its deal is contingent on Mylan not completing the Perrigo acquisition.

Mylan offered a new higher bid for Perrigo worth $32bn, composed of $60 in cash and 2.2 Mylan shares for each Perrigo share. The combined company would be owned 61.8% by Mylan shareholders with Perrigo owning the remainder. Perrigo quickly rejected the revised bid.

Mylan increased its offer for Perrigo once again. The new offer consists of $75 per share in cash and 2.3 Mylan ordinary shares for each Perrigo ordinary share ($232.23 total value per share). Mylan shareholders would own approximately 60.7% of the combined company on a fully diluted basis.

Panther Biotechnology Inc.

Faulk Pharmaceuticals Inc.

Panther Biotechnology Inc. acquired most of the assets of privately held Faulk Pharmaceuticals Inc. (drug conjugates for cancer and other diseases), including technology, patents, and candidates in development. (Apr.)

Panther will issues shares of its stock, and will also pay royalties on sales of commercialized products based on the assets it purchased. Faulk holds 23 patents (domestic and international), with more applications pending, on its ligand-drug conjugate technology that binds transferrin glycoproteins with chemotherapeutics to reduce toxic side effects and drug resistance. The lead compound Faulk brings to the table is TRFDOX, a doxorubicin conjugate that has shown positive activity in trials for ovarian cancer, leukemia, and angiosarcoma. Panther will submit applications for Phase II ovarian cancer trials and Phase Ia/Ib for lung cancer. It also gains projects for additional cancers as well as autoimmune, antiviral, and other diseases.

Teva Pharmaceutical Industries Ltd.

Mylan NV

On the same day that generics/OTC firm Perrigo Co. PLC's board unanimously rejected an unsolicited offer to be acquired by fellow public generics company Mylan NV for approximately $29bn, Mylan itself received an unsolicited proposal to be bought by Teva Pharmaceutical Industries Ltd. in a deal worth $40bn, or $82 per share (a 21% premium), evenly split between cash and Teva stock. Rumors about a Teva bid for Mylan surfaced in March 2015. (Apr.)

Teva's move for Mylan would be the most expensive acquisition ever for the Israeli company, surpassing its $9bn purchase of Barr Pharmaceutical in 2008. A proposal to buy Mylan comes at a time when Teva has shifted focus to certain therapeutic areas, namely respiratory and neurology, and reduced efforts in cancer and women's health. The deal also comes less than a week after the FDA approved Sandoz/Momenta's Glatopa (glatiramer), the first generic of Teva's top-selling multiple sclerosis peptide Copaxone, potentially eating into the over $4bn the product realizes in worldwide sales. Prior to Teva's official announcement of its intent to acquire, Mylan stated that it did not want to pursue a transaction with the Israeli company and was committed to remaining independent and moving forward with Perrigo, although that deal itself is now in question. Teva, which is making its proposal contingent on Mylan not completing the Perrigo acquisition, believes a Teva/Mylan combination would create the second-leading generics company in the industry in terms of 2015 estimated revenue at $29bn, behind Sandoz ($53bn) and ahead of Actavis ($22bn). Together, Teva and Mylan would have over 400 pending ANDAs, plus an improved infrastructure to produce complex generics and biosimilars. Mylan, founded in 1961, has a portfolio of 1.4k generics (mostly solid oral dosages and transdermal patches) and specialty medicines (respiratory and psychiatric diseases and allergies) sold in 145 countries. It is also a global producer of APIs. The company has made several transformative acquisitions in the last couple years, including Famy Care in women's health and Agila Specialties in generic injectables. In addition, Mylan paid $5.6bn for Abbott's developed markets specialty and branded generics business, helping Mylan to expand outside of the US. The Abbott deal was treated as a tax inversion, with Mylan redomiciling in the Netherlands. Mylan reported 2014 net earnings of $929.4mm on $7.7bn in revenues. At the end of 2014, the company had $226mm cash on hand. Investment Banks/Advisors: Barclays Bank PLC; Greenhill & Co. Inc. (Teva Pharmaceutical Industries Ltd.)

April 2015 update: Mylan's board unanimously rejected the unsolicited from Teva, which reiterated its commitment to the deal.

Alliances

4D Molecular Therapeutics LLC

Roche

4D Molecular Therapeutics LLC (4DMT) and Roche agreed to discover and develop adeno-associated virus (AAV) vectors for gene transfer. The California Institute for Quantitative Biosciences (QB3) facilitated the deal. (Apr.)

4DMT is responsible for using its Directed Vector Evolution (DVE) technology to identify and optimize the vectors for delivery of genes to any tissue or organ. According to secondary industry sources, Roche will license worldwide rights to the vectors for gene therapeutics delivery and conduct preclinical and clinical testing. The targeted indications weren't disclosed, only that they are an unmet need and are monogenic diseases. Roche hasn't been active in gene therapeutics dealmaking, and doesn't have any such candidates in its pipeline. 4DMT, a 2013 start-up, says that DVE's AAV vectors are more specific and efficient than first-generation vectors, and only affect targeted tissue while resisting immune clearance by evading pre-existing antibodies. The company's acting CSO David Schaffer, PhD, developed DVE at the University of California, Berkeley. Just a week prior to the Roche announcement, 4DMT signed a similar deal with Applied Genetic Technologies Corp. (AGTC) in ophthalmology. In addition, uniQure has exclusive rights to 4DMT's AAV vector technology for gene delivery to the liver or CNS. The current alliance, ironically, came on the same day that Celladon disclosed that its cardiovascular gene candidate Mydicar failed in Phase IIb after not meeting primary and secondary endpoints, a major blow to the gene therapy field (and one that sent the stocks of gene therapy developers like uniQure and AGTC tumbling down).

4SC AG

Menarini Group

Menarini Asia-Pacific Holdings Pte. Ltd.

4SC AG granted Menarini Asia-Pacific Holdings Pte. Ltd. exclusive rights to develop and sell its cancer therapy resminostat in Asia-Pacific countries, including China, South Korea, Australia, Thailand, and others, but excluding Japan where Yakult Honsha already has rights. (Apr.)

Prior to its acquisition by Takeda, Nycomed sold its oncology business to 4SC in 2009; that transaction included resminostat, an oral HDAC inhibitor which 4SC has since brought into Phase II trials for cancers including hepatocellular carcinoma (liver cancer; the main indication) and Hodgkin’s lymphoma, and Phase I for advanced colorectal cancer. (Yakult Honsha also has it in Phase II trials for non-small cell lung cancer.) Menarini could make a total of up to €95mm ($102mm) in payments to 4SC, comprised of an up-front fee and development, regulatory, and commercialization milestones, plus double-digit royalties.

Argos Therapeutics Inc.

Chongqing Lummy Pharmaceutical Co. Ltd.

Argos Therapeutics Inc. granted Chongqing Lummy Pharmaceutical Co. Ltd. and its Lummy (Hong Kong) Co. Ltd. subsidiary exclusive rights to develop, manufacture, and sell its Phase III renal cell carcinoma candidate AGS003 in China, Hong Kong, Taiwan, and Macau. (Apr.)

In the same territories, Lummy also gains exclusive rights to the Arcelis personalized immunotherapy technology, which it may use to develop additional candidates for other cancers including pancreatic, liver, lung, rectal, stomach, gastric, and esophageal. (The company additionally gets a right of first negotiation to apply Arcelis to infectious disease projects.) To seal the deal, Lummy and certain affiliates (Tianyi Lummy International and the China BioPharma Capital I Fund) took a 5% stake in Argos through the purchase of 1mm Argos shares at $10.11 apiece (a 14% premium) for $10mm, and agreed to buy another $10mm in shares following the release of interim data from the pivotal Phase III ADAPT trial currently underway with AGS003. Lummy could also pay up to $20mm in regulatory and sales milestones, plus royalties in the teens. Argos had previously licensed AGS003 to Kyowa Hakko Kirin in China, South Korea, Taiwan, and Japan, but rights were later returned when Kyowa reorganized its portfolio. Now Lummy picks up some of those rights, while Green Cross has a license to the compound in South Korea, and Medinet has an option to rights in Japan.

Arvinas Inc.

Merck & Co. Inc.

Two-year old Arvinas LLC penned its first major agreement, signing a multi-year deal with Merck & Co. Inc. to use the PROTAC protein degradation technology against targets selected by Merck. While Arvinas’ focus up until now has been using the platform for cancer, the companies note that several undisclosed therapy areas will be involved. (Apr.)

Merck will pay money up front, in addition to research funding and up to $434mm in research, development, regulatory, and sales milestones, plus tiered royalties. The Big Pharma has the option to expand the deal to include additional targets, for which it would pay more in milestones and royalties, as well as a separate up-front payment. PROTACs (proteolysis-targeting chimeras) are bifunctional small molecules that induce protein degradation by the body’s ubiquitin/proteasome system to rid the body of disease. Arvinas holds a license to the technology from Yale University, based on the research of Dr. Craig Crews (who is also an Arvinas founder and the company’s chief scientific advisor). Dr. Crews first focused on protein degradation when he was at Proteolix Inc., and helped discover the multiple myeloma drug Kyprolis (carfilzomib), which inhibits proteasome activity to prevent protein degradation. (Proteolix was later bought by Onyx, which was then purchased by Amgen in 2013.) Crews and Arvinas are now developing PROTACs to do the opposite--use the proteasome to target and degrade previously "undruggable" proteins.

Astellas Pharma Inc.

Potenza Therapeutics Inc.

Astellas Pharma Inc. and Potenza Therapeutics Inc. teamed up to discover and develop cancer immunotherapies that target immune checkpoint pathways, co-stimulatory signals, and regulatory T cells. (Apr.)

Potenza will head up drug discovery and deliver candidates to Astellas, which will handle clinical development and gets exclusive rights to commercialize resulting therapeutics. Astellas will make an equity investment in Potenza and pay an option fee, research funding, and milestone payments. In addition, Astellas receives the option to buy Potenza outright should pre-determine goals be met at the end of the alliance. Potenza was founded last year and is disclosing little about its technology except to say it is focused on disrupting the mechanisms that cancer cells use to evade detection and destruction by the immune system. Astellas Venture Management participated in Potenza’s $38mm Series A in late-2014.

Boehringer Ingelheim GMBH

Hydra Biosciences Inc.

Boehringer Ingelheim GMBH and Hydra Biosciences Inc. teamed up for the second time in a year, aiming to identify transient receptor potential (TRP) ion channel inhibitors for renal diseases. BI holds worldwide development and commercialization rights to resulting drugs. (Apr.)

Hydra gets an up-front fee, research funding, milestones, and tiered royalties. In their April 2014 deal, the companies also focused on TRP blockers (specifically those interacting with TRP C4/5) in the CNS area, which has also been the focus of most of Hydra's other previous alliances (including with Pfizer and Merck's Cubist). In the new BI agreement, Hydra will test the potential of its TRP agents in renal disorders, including chronic kidney disease. BI doesn't have much activity in this therapeutic area. Under its 2011 diabetes deal with Lilly, BI held an option on Phase II LY2382770 (diabetic nephropathy), but Lilly terminated development as of last year.

Bristol-Myers Squibb Co.

uniQure NV

In its first major gene therapy deal, Bristol-Myers Squibb Co. received exclusive rights to uniQure NV's gene therapy technology for use against ten cardiovascular targets, including the calcium-binding protein S100A1 (BMS will have rights to the preclinical S100A1 program for congestive heart failure). (Apr.)

While BMS's current leading products by sales are in infectious diseases and oncology, the company's Factor Xa inhibitor Eliquis (apixaban; partnered with Pfizer) for the prevention of stroke and systemic embolism is forecasted by Datamonitor to reach nearly $1bn in sales this year, following a slow start on the market over the past three years due to competitive anti-coagulants. As a result, cardiovascular could become an increasingly important area of focus for BMS. UniQure gets $50mm up front; a $15mm milestone upon selection of three targets (including S100A1) within three months; a $32mm equity investment through the sale of approximately 946k uniQure shares for $33.84 (a 35% premium), giving BMS a 4.9% stake; up to $254mm in R&D and regulatory milestones for S100A1; up to $217mm in R&D and regulatory milestones for each other gene therapy; sales milestones; and single-to-double-digit sales royalties. BMS may increase its stake by 5% before December 31, 2015 by purchasing shares at a 10% premium. In addition, the company received two warrants to buy even more shares (triggered by adding new targets to the deal), which would bump its stake up by another 10%. UniQure is in charge of discovery activities and will use its vector and insect-cell technologies to manufacture clinical and commercial supplies (the partners entered into a supply agreement). BMS is responsible for all R&D expenses and will lead development, regulatory efforts, and commercialization. UniQure got the adeno-associated virus S100A1 gene replacement agent, which is also known as InoCor (AAV-S100A1), through its $4mm acquisition of InoCard last year. S100A1 regulates myocardial contractility, and InoCor is believed to work by restoring sarcoplasmic reticulum calcium handling. Phase I trials are expected to start next year.

Celgene Corp.

AstraZeneca PLC

MedImmune LLC

Celgene Corp. licensed global rights to AstraZeneca PLC and MedImmune LLC's MEDI4736 (durvalumab), which it will develop and sell for blood cancers. (Apr.)

Celgene paid $450mm up front and will be responsible for all clinical trials and commercialization in the licensed indications. (It also funds all development costs until December 31, 2016, and will then shoulder 75% of the expenses after that point.) AZ, which will manufacture the compound and book sales, will pay initial royalties of 70% on global sales, with the rate gradually decreasing to 50% over the four years following the first commercial sale. MEDI4736 is monoclonal antibody anti-PD-L1 inhibitor that works by blocking signals from PD-L1 that would otherwise direct tumor cells to evade detection by the immune system. It is being developed in a variety of trials (Phase I-III) for solid tumors, and in Phase I for blood cancers. Celgene plans to investigate its use both as a monotherapy and in combination with some of its own candidates to treat non-Hodgkin’s lymphoma, multiple myeloma, and myelodysplastic syndromes. The scope of the deal could also be expanded later to include other assets. AZ and MedImmune seem highly focused on MEDI4736 lately. On the same day as the Celgene deal was announced, MedImmune also licensed rights to Innate Pharma's IPH2201, which MedImmune will study in combination with MEDI4736. (AZ paid $250mm for that asset, and could spend up to $1bn in milestones.) MEDI4736 is also being investigated in combination with other partners' projects, including Juno Therapeutics’ anti-CD19 CART therapy (announced earlier this month) and Immunocore’s IMCgp100 for metastatic melanoma.

Celgene Corp.

Mesoblast Ltd.

Celgene Corp. bought $A58.5mm ($44mm) of Mesoblast Ltd. shares (15.3mm shares at $A3.82, an 11% premium), for a 4.5% stake in the company. (Apr.)

Celgene also gets a six-month right of first refusal regarding Mesoblast’s mesenchymal lineage adult stem cell compounds in development for graft versus host disease (GVHD), cancer, inflammatory bowel diseases, and organ transplant rejection. One of the programs presumably included in the deal is Prochymal (JR031), a mesenchymal stem cell (MSC) product available in the US (under the Expanded Access Program) and conditionally approved in other markets for children with acute GVHD. (JCR Pharmaceuticals has rights in Japan.) Mesoblast gained Prochymal and other MSC assets from Osiris Therapeutics in 2013. The deal with Mesoblast has the potential to expand Celgene’s regenerative medicine offerings.

Curadev Pharma Pvt. Ltd.

Roche

Curadev Pharma Pvt. Ltd. licensed Roche exclusive rights to develop its preclinical indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO) immune checkpoint inhibitor, which may be used as either as a monotherapy or in combination with a Roche oncology drug. The partners will also collaborate on R&D of IDO1/TDO blockers. (Apr.)

Roche pays $25mm up front, and for the first product, up to $530mm in total milestones and escalating double-digit royalties. The Big Pharma is also responsible for additional milestones and royalties for additional drugs. Roche will provide research funding and cover future R&D, manufacturing, and commercialization costs. Roche had been testing a combination of its metastatic melanoma drug vemurafenib with BMS's CTLA-4 inhibitor Yervoy (ipilimumab), but the companies halted studies in 2013 because of toxic liver side effects. Since then, Roche has teamed up with Immatics Biotechnologies GMBH, whose XPRESIDENT technology might be used to develop combinations of vaccines and immune modulators or checkpoint inhibitors. In addition, Genentech has done a couple deals in the immune checkpoint area with Array Biopharma (Checkpoint kinase 1 (ChK-1)) and NewLink Genetics (IDO1 and combination IDO/TDO).

Dr. Reddy's Laboratories Ltd.

UCB Group

UCB Group sold a portfolio of drugs it markets in India to Dr. Reddy’s Laboratories Ltd. for $130mm, on what the companies call a “slump sale” basis. (Apr.)

About 350 of UCB’s employees associated with the products also transfer to Dr. Reddy’s. Included in the deal are the anti-allergy drugs Atarax (hydroxyzine), Zyrtec (cetirizine), and Xyzal/Xyzal M (levocetirizine), as well as Nootropil (piracetam) for dementia and vertigo. Combined, the portfolio brought in about $25mm in sales during 2014 in India, Nepal, Sri Lanka, and Maldives. Dr. Reddy’s claims that the product purchase will expand the company’s presence in the areas of dermatology, respiratory conditions, and pediatric diseases, while UCB looks forward to the divestiture affording the company the opportunity to focus efforts on its neurology assets in India.

Esperas Pharma Inc.

Eli Lilly & Co.

TVM Life Science Ventures VII co-invested with Fonds de solidarité FTQ to establish Esperas Pharma Inc., a company whose sole purpose will be to develop a cancer compound originally discovered by Eli Lilly & Co. (Apr.)

The specific candidate was not revealed, but it has completed GLP toxicology studies. Esperas plans to begin its clinical trials during the first quarter of 2016, initially studying the project both alone and in combination with gemcitabine in women with triple-negative breast cancer, though additional cancer indications could be pursued later. If and when it reaches human proof-of-concept, Lilly has an option to acquire the compound. Esperas is located in Québec and is headed by CEO Caroline Fortier, along with CFO Mark Cipriano.

Eyenovia Inc.

Senju Pharmaceutical Co. Ltd.

Eyenovia Inc. licensed Senju Pharmaceutical Co. Ltd. exclusive Asian rights to develop and sell its microdrop therapeutics for eye diseases. (Apr.)

Senju is in charge of R&D. The company concurrently joined as an investor in Eyenovia's Series A financing, which was completed in October 2014. In the last two years, Senju has also gotten rights to Insite's AzaSite line of ocular antibiotics and to Allegro's Luminate for vascular eye diseases. In the new deal, Senju is expected to take advantage of Eyenovia's microdrop technology, which Eyenovia acquired from Corinthian Ophthalmics last year. Eyenovia says microdrops would provide a major improvement and advantage over traditional eye droppers, which have been used as the standard delivery mechanism in the treatment of multiple ophthalmic diseases. Drops delivered via the conventional eye dropper, according to Eyenovia, can administer eight times more drug than needed, leading to potential toxicity and other side effects. In comparison, the size, ejection, and dispersion of the company's microdrops are controlled by piezoelectric technology, helping to improve bioavailability, efficacy, and safety. Eyenovia also plans to enhance its delivery device with smart sensors and monitoring technology that will increase patient compliance.

H. Lundbeck AS

Ovid Therapeutics Inc.

H. Lundbeck AS licensed Ovid Therapeutics Inc. exclusive worldwide rights to develop and sell the highly selective extrasynaptic GABA-A agonist gaboxadol for the orphan diseases Angelman and Fragile X syndromes. Ovid renamed the candidate OV101. (Apr.)

Lundbeck received a minority stake in Ovid and will get milestones and sales royalties. In 2004, Lundbeck partnered gaboxadol (MK0928) with Merck & Co. in the US, where the companies planned to co-promote the drug candidate (they later expanded the deal to Japan). At the time, gaboxadolwas in Phase III for insomnia, but in 2007, they terminated the agreement because of poor clinical results. Ovid, which was founded last year, is now hoping to get gaboxadol to market in two new indications. Angelman syndrome is a rare neurological and genetic disorder that can cause development delay, lack of speech, and seizures. Fragile X is also a genetic condition that can lead to developmental problems including learning disabilities and cognitive impairment. Both diseases are characterized by synaptic dysfunction, which can reduce GABA, therefor a GABA-A agonist such as gaboxadol might have potential. In addition, gaboxadol is able to restore tonic inhibition, which is also a result of synaptic dysfunction. Ovid plans to start a Phase II trial in the Angelman indication next year, followed by Phase II in Fragile X. In animal studies, OV101 was shown to correct the motor deficit seen in Angelman syndrome. The start-up also has candidates in its pipeline for Lewy body dementia, Dravet syndrome, and Prader-Willi syndrome.

Ichor Medical Systems Inc.

Johnson & Johnson

Janssen Pharmaceuticals Inc.

Janssen Pharmaceuticals Inc. will use Ichor Medical Systems Inc.’s TriGrid electroporation technology as a delivery vehicle for its own DNA-based vaccines for chronic hepatitis B. (Apr.)

Janssen will pay money up front, R&D funding, and development and sales milestones; total payments could reach up to $85mm. Ichor will also receive sales royalties. Janssen is responsible for all commercialization costs and manufacturing and distribution expenses for Ichor’s TriGrid delivery system. DNA delivery via traditional injections is often not efficient and results in poor immune responses. Electroporation uses brief electrical pulses that alter cell membranes and facilitate the entry of DNA into cells.

Innate Pharma SA

AstraZeneca PLC

MedImmune LLC

AstraZeneca PLC and its biologics division MedImmune LLC licensed exclusive global rights to develop and sell a cancer therapy combining their MEDI4736 with Innate Pharma SA’s IPH2201. AZ also gets access to IPH2201 as a monotherapy and combo treatment in other undisclosed areas. (Apr.)

Innate gets $250mm up front, $100mm before the start of Phase III trials, up to $925mm in regulatory and sales milestones. It also gets co-promotion rights in Europe for a 50% profit share there. AZ books sales, and pays double-digit royalties. The companies have already stated their development plan, with Phase II trials of the combination treatment upcoming, multiple Phase II trials by Innate with IPH2201 as a monotherapy and in combination with currently approved drugs across a variety of cancer types, and the development of associated biomarkers. The combo therapy would create a cancer treatment addressing multiple immune pathways; AZ/MedImmune’s MEDI4736 (in Phase I-III trials for a number of solid and blood cancers) is an anti-PD-L1 immune checkpoint inhibitor, while IPH2201 is a humanized IgG4 antibody against NKG2A, a checkpoint receptor that inhibits the functions of natural killer and cytotoxic T-cells. IPH2201 was previously licensed to Innate's partner Novo Nordisk, which had been developing it for rheumatoid arthritis. Innate took back rights last year, however, to pursue the candidate's potential in immuno-oncology. The deal is the second involving MEDI4736 announced on the same day. AZ also penned an alliance that grants Celgene global rights to develop and sell MEDI4736 specifically for blood cancers. (Celgene paid $450mm up front for the rights.)

Innate Pharma SA

Sanofi

Innate Pharma SA agreed to apply its antibody-drug conjugate technology to potentially develop new cancer treatments for Sanofi. (Apr.)

Innate’s site-specific ADC platform uses the bacterial transglutaminase (BTG) enzyme to attach a linker molecule to an antibody, while a cytotoxin is attached to the linker. The companies will explore combinations of Sanofi’s antitumor antibodies with the BTG linking technology; Sanofi-Aventis Recherche & Développement (Sanofi’s R&D unit) will evaluate conjugations to enhance pharmacokinetics, efficacy, and safety, and holds an option to license the technology from Innate.

Juno Therapeutics Inc.

Novartis AG

St. Jude Children's Research Hospital

University of Pennsylvania

Partners Novartis AG and the University of Pennsylvania settled a nearly three-year-old lawsuit with Juno Therapeutics Inc. (which had settlement authority through its 2013 agreement with St. Jude Children's Research Hospital) related to chimeric antigen-receptor modified T (CART) cell IP. The parties will dismiss all claims in legal proceedings. (Apr.)

In December 2013 the Fred Hutchinson Cancer Research Center, Memorial Sloan Kettering Cancer Center, and Seattle Children’s Research Institute founded Juno, which received an initial $120mm in Series A funding (later expanded to a total of $176mm) from Arch Venture Partners and Alaska Permanent Fund to support work on engineered memory T-cells, including CART cell and high-affinity T-cell receptor therapeutics. At the same time it launched, Juno also got exclusive worldwide rights to St. Jude's patented CART technology. Juno has several CART candidates that target the CD19 antigen, same as Novartis' Phase II CTL019 (CART019), to which the Big Pharma has held rights (as well as CART technologies) from the University of Pennsylvania since 2012. In March 2013 (before Juno was founded), UPenn had sued St. Jude seeking a declaratory judgment that the university didn't infringe St. Jude’s US patent 8,399,645 ("Chimeric receptors with 4-1BB stimulatory signaling domain") and that the patent claims were invalid. UPenn had produced some of that early research. The courts allowed Juno to intervene in the case, as Juno held a financial interest in upholding the validity of St. Jude's patent to aid in protecting its investments in the CART area. In November 2013, the courts denied UPenn's motion for partial summary judgment regarding the validity of the '645 patent. In January 2014, Novartis similarly got involved, on UPenn's behalf unsurprisingly, filing a motion to intervene. Separately, in July 2012, St. Jude filed a complaint saying UPenn had breached two materials transfer agreements covering St. Jude's provision of biological material to UPenn and the university's director of translational research Carl June, MD, who led the team that developed T-cells expressing the CART19 receptor, which binds to CD19. St. Jude claimed that its researcher Dario Campana, MD, PhD, had created an anti-CD19 chimeric T-cell receptor construct involved in the material breach. St. Jude also claimed that it provided UPenn with an innovative molecular receptor covered under the '645 patent. This complaint was later consolidated with the March 2013 lawsuit. Under the current settlement, Novartis pays Juno $12.25mm up front; clinical, regulatory, and commercialization milestones; mid-single-digit royalties (Strategic Transactions estimates 5%) on US sales of drugs related to the disputed contract and patent claims; and a low double-digit percentage (Strategic Transactions estimates 30%) of the royalties Novartis pays to UPenn for global net sales of those products. St. Jude will share these payments. In return, Novartis gets nonexclusive rights to Juno's patents, including '645, covering all therapeutic, diagnostic, preventative, and palliative uses. Should Juno achieve any milestones before Novartis, the total milestone payment is cut in half. If June meets any milestones after Novartis, Juno will reimburse Novartis 50% of any milestone payment previous made by Novartis.

Sanofi

Sanofi Pasteur

VBI Vaccines Inc.

VBI Vaccines will use its Lipid Particle Vaccine (LPV) technology to enhance one of Sanofi Pasteur’s key vaccine candidates. Neither the compound nor its therapy area was disclosed. (Apr.)

Sanofi paid money up front and will reimburse VBI monthly for R&D costs, subject to a maximum cap. Sanofi retains an option, during the first three months of the nine-month feasibility study, for a royalty-bearing global license to the LPV platform for use in its other vaccines outside of the licensed field. Many vaccines and biologics lose potency and become ineffective if not shipped and stored in a constant temperature that is slightly above freezing. LPV uses a proprietary process involving lipids which surround and enclose the antigen in the vaccine, providing for thermostability up to 40°C/104°F. In-house, VBI completed proof-of-concept of LPV vaccines for influenza, rabies, and MMR.

Taxus Cardium Pharmaceuticals Group

Angionetics Inc.

Dr. Reddy's Laboratories Ltd.

Taxus Cardium Pharmaceuticals Group's Angionetics Inc. subsidiary licensed Dr. Reddy's Laboratories Ltd. exclusive rights to co-develop, market, and sell Generx (Ad5FGF4; alferminogene tadenovec), in Phase III for refractory angina and myocardial ischemia due to cardiac microvascular insufficiency (CMI) in certain territories. (Apr.)

Markets included in the agreement are Russia, the Commonwealth of Independent States, Venezuela, Vietnam, and Myanmar. Dr. Reddy’s also has the right of first refusal to negotiate exclusive rights to market and sell Generx in over 30 countries in Latin America and the Association of Southeast Asian Nations. Angionetics retains full commercial rights for the angiogenic microvascular gene therapy in North America, Europe, Japan, China, the Middle East, and Africa. The company plans to become an independent entity and will externally finance the US and international Phase III trials and explore other indications for Generx. Dr. Reddy's will co-develop the compound with Angionetics, assist with product registrations and regulatory compliance, and help with local country patient recruitment. The partnership involves cost-sharing for a planned Phase IV post-marketing trial to expand product labeling, and volume-based sales royalties. In October 2005, Taxus Cardium (then known as Cardium Therapeutics) got exclusive global right to Generx and other cardiovascular growth factor compounds from Schering (now Bayer).

Financings

Adaptimmune Therapeutics PLC

Less than a year after closing its $104mm Series A round (the largest Series A in 2014), UK-based Adaptimmune Therapeutics PLC (T-cell therapy) filed for its US initial public offering. The company plans to sell 9.4mm ADSs (representing 56.2mm ordinary shares) for $15-17. (Apr.)

Investment Banks/Advisors: Bank of America Merrill Lynch; Cowen & Co. LLC; Guggenheim Partners LLC; Leerink Partners LLC

Aduro BioTech Inc.

Cancer immunotherapy firm Aduro Biotech Inc. netted $127mm its initial public offering of 8.1mm shares (including the overallotment) for $17. The company had planned to sell 5mm shares at $14-16. Existing investors bought $22.5mm in IPO shares, including JJDC ($10mm). (Apr.)

Investment Banks/Advisors: Bank of America Merrill Lynch; Canaccord Genuity Inc.; Leerink Partners LLC; William Blair & Co.

Akebia Therapeutics Inc.

Akebia Therapeutics Inc. (developing hypoxia inducible factor-prolyl hydroxylase inhibitors) netted $64.9mm by publicly selling 8.4mm common shares (including the overallotment) at $8.25. The company plans to use the money for Phase III trials of AKB6548 for anemia related to chronic kidney disease, and Phase I cancer studies of AKB6899. (Apr.)

Investment Banks/Advisors: Brean Capital LLC; JMP Securities LLC; Morgan Stanley & Co.; Needham & Co. Inc.; UBS Investment Bank

aTyr Pharma Inc.

Just a week after announcing its $76mm Series E round, aTyr Pharma Inc. (physiocrine-based therapies for rare diseases) filed for its initial public offering. (Apr.)

April 2015 update: The company set terms: 5.36mm shares between $13-15.

Investment Banks/Advisors: BMO Financial Group; Citigroup Inc.; JP Morgan & Co.; William Blair & Co.

Biodel Inc.

Biodel Inc. netted $28.1mm through the follow-on public sale of 32.6mm common shares at $0.92 each. Funds will help finish clinical trials and submit the NDA for its glucagon emergency management device for treating diabetics with severe hypoglycemia. Some money has also been earmarked for continued clinical trials of Phase II BIOD531, a concentrated ultra-rapid-acting insulin formulation. (Apr.)

Investment Banks/Advisors: Ladenburg Thalmann & Co. Inc.; Roth Capital Partners; William Blair & Co.

Blueprint Medicines Corp.

Blueprint Medicines Corp. (founded in 2011; developing kinase inhibitors for genetically defined diseases) grossed $146.7mm through its initial public offering of 8.15mm shares at $18. The company had previously announced plans to sell 7.2mm shares between $15-17. (Apr.)

Investment Banks/Advisors: Wedbush PacGrow Life Sciences; Cowen & Co. LLC; Goldman Sachs & Co.; JMP Securities LLC

Carbylan Therapeutics Inc.

Carbylan Therapeutics Inc. netted $69.5mm through its initial public offering of 15mm common shares (including the overallotment) at $5. In January, the company stated it planned to sell 5.8mm shares between $12 and $14. (Apr.)

Investment Banks/Advisors: JMP Securities LLC; Leerink Partners LLC; Wedbush PacGrow Life Sciences

Cellceutix Corp.

Cellceutix Corp. entered into a three-year $30mm stock purchase agreement with Aspire Capital Fund LLC. Aspire previously provided the company with $30mm in two similar transactions. (Apr.)

Cerulean Pharma Inc.

Cerulean Pharma Inc. (nanoparticle-drug conjugates for cancer) netted $37.9mm by publicly selling 6.7mm shares (including the overallotment) at $6. Some of the money will be used for CRLX101, in Phase II trials for relapsed renal cell carcinoma, relapsed ovarian cancer, and neoadjuvant rectal cancer, and for CRLX301, in Phase I for solid tumors. (Apr.)

Investment Banks/Advisors: Barclays Bank PLC; Canaccord Genuity Inc.; JMP Securities LLC; Leerink Partners LLC; Wedbush PacGrow Life Sciences

Cidara Therapeutics Inc.

Antifungal-focused Cidara Therapeutics Inc. netted $71.4mm in its initial public offering of 4.8mm common shares at $16, the high end of its intended range. (Apr.)

Investment Banks/Advisors: BTIG LLC; Jefferies & Co. Inc.; Leerink Partners LLC; Needham & Co. Inc.; Wedbush PacGrow Life Sciences

Cipher Pharmaceuticals Inc.

Cipher Pharmaceuticals Inc. (reformulates existing products; focused on cardiology, neurology, and dermatology markets) raised $100mm by selling five-year 10.25% senior secured notes to Athyrium Capital Management investment funds. (Apr.)

Investment Banks/Advisors: Piper Jaffray & Co.

Clinigen Group PLC

Clinigen Group PLC netted $200mm (£131.6mm) through a new ordinary share placing of 27mm shares at $7.60, a 5% discount. The company expects to use the proceeds from the placing, along with a debt facility, to finance its pending acquisition of Idis Group Holdings Ltd. Concurrently, Clinigen issued to an Idis investor 153k ordinary shares. (Apr.)

Investment Banks/Advisors: Numis Securities Ltd.; Peel Hunt LLP

Collegium Pharmaceutical Inc.

Collegium Pharmaceutical Inc. (abuse-deterrent CNS treatments) filed for its IPO, planning to sell 5.8mm shares at $12-14. (Apr.)

Investment Banks/Advisors: Jefferies & Co. Inc.; Needham & Co. Inc.; Piper Jaffray & Co.; Wells Fargo Securities LLC

Conatus Pharmaceuticals Inc.

Conatus Pharmaceuticals Inc. (hepatic diseases) netted $21.8mm in a follow-on public offering of 4mm shares (including the overallotment) at $5.75. It will use the money to continue developing and prep for registration trials of its Phase II pan-caspase protease inhibitor emricasan in post-liver transplant HCV clearance and liver cirrhosis (including with portal hypertension). (Apr.)

Investment Banks/Advisors: Roth Capital Partners; Stifel Nicolaus & Co. Inc.

Dyax Corp.

Through a follow-on public offering, Dyax Corp. (in-house development of treatments for hereditary angioedema; out-licenses phage display technology) netted $216mm by selling 8.5mm shares (including the overallotment) for $27. The company will spend the money on DX2930, a Phase I antibody to prevent hereditary angioedema; candidates for other plasma-kallikrein-mediated (PKM) disorders and additional non-PKM orphan diseases; and to pay back a loan from LFRP Investors. (Apr.)

Investment Banks/Advisors: Bank of America Merrill Lynch; Cowen & Co. LLC; Needham & Co. Inc.; RBC Capital Markets; Wedbush PacGrow Life Sciences

Egalet Corp.

JMP Securities and Guggenheim Securities bought $60mm ($36mm and $24mm, respectively; $56mm net) in Egalet Corp. (pain products) convertible debt. (Apr.)

Foamix Pharmaceuticals Ltd.

In a follow-on public offering, Foamix Pharmaceuticals Ltd. (topical foam treatments for moderate-to-severe acne and other dermatological conditions) netted $56.4mm through the sale of 6.4mm shares for $9.30. (Apr.)

Investment Banks/Advisors: Barclays Bank PLC; Cowen & Co. LLC; Guggenheim Partners LLC; Oppenheimer & Co. Inc.

Gelesis Inc.

Metabolic-focused Gelesis Inc. filed for its initial public offering. (Apr.)

April 2015 update: The company plans to offer 4mm shares between $12 and $14 each.

Investment Banks/Advisors: Guggenheim Partners LLC; Piper Jaffray & Co.; Stifel Nicolaus & Co. Inc.

Hansa Medical AB

Hansa Medical AB (transplant rejection therapeutics) raised SEK246mm ($28mm) through a preferential and non-preferential rights issue. Stockholders subscribed to a total of 6.5mm shares. (Apr.)

Horizon Pharma PLC

Horizon Pharma PLC (markets therapies for pain, arthritis, and rare diseases) netted $476mm through the public sale of 17.65mm common shares (including the overallotment) at $28.25. (The company originally planned to sell 12mm shares.) The money will partially fund Horizon's $960mm acquisition of Hyperion announced last month. (Apr.)

Investment Banks/Advisors: Citigroup Inc.; Cowen & Co. LLC; Jefferies & Co. Inc.; Morgan Stanley & Co.

Immune Design Corp.

Immune Design Corp. (immunotherapies for cancer, allergies, and infectious diseases) netted $74.7mm by publicly selling 3mm shares at $26.50. Proceeds will fund Phase I and II trials of CMB305 (solid tumors) and G100 (Merkel cell carcinoma and sarcoma), and will also go toward initiating clinical development of a new candidate based on the ZVex in vivo cytotoxic T-cell generating platform. (Apr.)

Investment Banks/Advisors: Cowen & Co. LLC; Jefferies & Co. Inc.; Leerink Partners LLC; Wells Fargo Securities LLC

KemPharm Inc.

In its initial public offering, KemPharm Inc. (creates new molecular entities via prodrug technology) netted $52.1mm by selling 5.1mm shares (above the 4mm planned) for $11, below its $12-14 price range. Existing investor Deerfield agreed to buy 500k of the shares. (Apr.)

Investment Banks/Advisors: Canaccord Genuity Inc.; Cowen & Co. LLC; Oppenheimer & Co. Inc.; RBC Capital Markets

Lipocine Inc.

Lipocine Inc. (liposome-based drug delivery for men's and women's health therapies) netted $28.4mm through the public sale of 4.65mm shares at $6.50. (Apr.)

MabVax Therapeutics Holdings Inc.

Opko Health Inc. and its chairman and CEO Dr. Phillip Frost invested $11.6mm in MabVax Therapeutics Holdings Inc. (vaccines and mAbs for cancer) through the purchase of 15.5mm units at $0.75 (a 64% discount). Each unit consists of a common share and a 30-month warrant to buy half a common share at $1.50. Proceeds will fund initiation of Phase I trials for MabVax's HuMab 5B1 antibody as both a diagnostic and therapeutic for pancreatic and colon cancers. (Apr.)

Investment Banks/Advisors: Laidlaw & Co.

Matinas BioPharma Holdings Inc.

Matinas BioPharma Holdings Inc. (lipid-based therapies for infectious, cardiovascular, and metabolic conditions) netted $8.5mm through the sale of 20mm units at $0.50 each (a 26% discount) to company board members and management and affiliates of Aegis Capital Corp.’s SternAegis Ventures, which was the placement agent. One unit consists one common share and a five-year warrant to buy a share at $0.75. (Apr.)

Investment Banks/Advisors: Aegis Capital Corp.

Merus Labs International Inc.

Merus Labs International Inc. (markets products for thromboembolic disorders, urinary conditions, and infections) netted $Cdn57mm ($45.3mm) from a bought deal financing of 19.7mm shares at $Cdn3.05. (Apr.)

Investment Banks/Advisors: Canaccord Genuity Inc.; Clarus Securities ; Cormark Securities Inc.; GMP Securities; Laurentian Bank Securities; TD Securities Inc.

Northwest Biotherapeutics Inc.

Northwest Biotherapeutics Inc. (dendritic cell-based cancer vaccines) closed the first tranche of a $40mm private placement agreement with Woodford Investment Management. The company initially sold 1.6mm common shares at $7.40 (a slight discount) for proceeds of $11.5mm, and by the end of April, expects the final closing of 3.8mm shares (at the same price) to bring in another $28.5mm. This is Woodford's second equity investment in Northwest; it bought $25mm in shares late last year. (Apr.)

Opexa Therapeutics Inc.

Opexa Therapeutics Inc. (personalized immunotherapies) netted $12.8mm through a rights offering by issuing 25.1mm units (including oversubscriptions) at $0.55. (Stockholders subscribed to a total of 25.1mm shares.) (Apr.)

Investment Banks/Advisors: Maxim Group LLC; National Securities Corp.

Pernix Therapeutics Holdings Inc.

Institutional investors bought $130mm (upsized from $120mm) in Pernix Therapeutics Holdings Inc. (branded and generic products) six-year 4.25% notes, which convert into common at a rate of 87.2030 per $1k principal amount of notes (or $11.47 each; the company's stock is currently averaging $10.35). (Apr.)

Prothena Corp. PLC

Antibody developer Prothena Corp. PLC netted $115mm by publicly selling 3.3mm shares at $37. The company will use the proceeds to prepare for the anticipated commercialization of NEOD001 (in Phase III for AL amyloidosis, for which it has fast track designation), and R&D on other candidates including Phase I PRX002 (partnered with Roche) for Parkinson's, PRX003 in multiple indications including psoriasis, and other programs focused on misfolded proteins. (Apr.)

Investment Banks/Advisors: Credit Suisse Group; Ladenburg Thalmann & Co. Inc.; LifeSci Capital LLC; Oppenheimer & Co. Inc.; RBC Capital Markets; UBS Investment Bank; Wedbush PacGrow Life Sciences

Raptor Pharmaceutical Corp.

Orphan disease therapies developer Raptor Pharmaceutical Corp. netted $92.4mm through the follow-on sale of 10.9mm common shares (including the overallotment) at $9 each. (Apr.)

Investment Banks/Advisors: Citigroup Inc.; Cowen & Co. LLC; JMP Securities LLC; Janney Montgomery Scott Inc.; Leerink Partners LLC

SAGE Therapeutics Inc.

SAGE Therapeutics Inc. (rare neurological disease treatments targeting GABAA and NMDA receptors) netted $113mm through the follow-on public offering of 2.3mm shares at $52.50. The company plans to spend more than half of the proceeds ($60-65mm) on the Phase III trial and NDA preparation of SAGE547 in super-refractory status epilepticus, and $10mm on Phase I for SAGE 217 in orphan epilepsies, such as Dravet syndrome and Rett syndrome. (Apr.)

Investment Banks/Advisors: Cowen & Co. LLC; Goldman Sachs & Co.; JP Morgan & Co.; Leerink Partners LLC

SanBio Co. Ltd.

Regenerative medicine company SanBio Co. Ltd. grossed Y8bn ($67mm) in its IPO on the Mothers market of the Tokyo Stock Exchange, selling 4mm shares for Y2k. (Apr.)

Investment Banks/Advisors: Mizuho Bank Ltd.; Nomura Securities International Inc.; SBI Securities Co. Ltd.; SMBC Nikko Securities Inc.

Scynexis Inc.

Scynexis Inc. netted $33.66mm through a follow-on offering of 4.68mm common shares at $7.70 each. Some of the funds will support ongoing clinical development of IV and oral formulations of SCY078 for invasive fungal infections. (Apr.)

Investment Banks/Advisors: Canaccord Genuity Inc.; JMP Securities LLC; Needham & Co. Inc.; RBC Capital Markets

StemCells Inc.

StemCells Inc. (human neural cell treatments for spinal cord injury, retinal disorders, and neurodegenerative diseases) netted $23.5mm in a follow-on public offering of 35.7mm shares for $0.70. Investors also received five-year warrants to buy up to 26.8mm shares at $0.85. (Apr.)

Investment Banks/Advisors: Chardan Capital Markets; Maxim Group LLC

Trillium Therapeutics Inc.

Trillium Therapeutics Inc. (immuno-oncology) netted $51.8mm through the public sale of common and preferred shares. The company issued 1.75mm common shares (including the overallotment) at $19.50, and to existing shareholders whose purchase of common shares would result in beneficial ownership exceeding 4.99%, issued 1.1mm Series II non-voting preferred shares (convertible into common). Proceeds will fund development of SIRPaFc, a fusion protein in IND-enabling studies for acute myeloid leukemia and other blood cancers. (Apr.)

Investment Banks/Advisors: Cowen & Co. LLC; Leerink Partners LLC; Oppenheimer & Co. Inc.

uniQure NV

Days after getting $47mm up front from Bristol-Myers Squibb Co. in a ten-target cardiovascular deal (including a $32mm equity investment), uniQure NV netted $83.2mm by publicly offering 3mm shares for $29.50. (Apr.)

Investment Banks/Advisors: Cowen & Co. LLC; HC Wainwright & Co.; Leerink Partners LLC; Oppenheimer & Co. Inc.; Piper Jaffray & Co.

XBiotech Inc.

XBiotech Inc. netted $72.2mm in its initial public offering of 4mm common shares at $19 each. (Apr.)

Investment Banks/Advisors: WR Hambrecht & Co.

RESEARCH, ANALYTICAL EQUIPMENT & SUPPLIES

Mergers & Acquisitions

Roche

Roche Sequencing

CAPP Medical

Roche Sequencing acquired private cancer research start-up CAPP Medical. (Apr.)

CAPP was founded in 2013 by Stanford University oncologists and former industry executives to develop a next-generation sequencing technology that can noninvasively detect, isolate, and quantify circulating tumor DNA (ctDNA) in blood, as opposed to a more invasive/traditional tissue biopsy. CAPP's method is currently only allowed for use in research (not in diagnostics), but has potential in cancer drug selection and tumor monitoring. The acquisition builds on two other deals that Roche has signed this year. In January the company took the majority stake in Foundation Medicine and established a five-year R&D collaboration in which the companies will advance multiple programs, including one in ctDNA. The following month, Roche bought Signature Diagnostics, which has biobanks that provide the basis for development of circulating cell-free DNA (cfDNA) tests in colorectal, lung, and other cancer types.