Lessons In Leadership And Biotech Growth From Rallybio CEO Martin Mackay
Executive Summary
Veteran pharma leader Martin Mackay, CEO of Rallybio, recently spoke with In Vivo about building a new company on the cusp of retirement, what drives him, how he leads and what he is excited about in the company’s pipeline.
It is an understatement to say that Martin Mackay is an industry veteran. The Rallybio Corp. CEO entered the field at the age of 16, later to return to advanced level studies. As he likes to note, he has had 31 bosses over his career, but has notably held top positions himself, at Alexion Pharmaceuticals Inc., AstraZeneca PLC and Pfizer Inc., where he helped develop and commercialize several ultra-rare and ultra-orphan therapies.
After a brief stint as a retiree, Mackay co-founded New Haven, CT-based Rallybio, a rare disease-focused biotech. He has shepherded the company into two significant co-development partnerships, several asset acquisitions and helped the company raise $182m before going public in the summer of 2021 and raising another $93m. (Also see "Rallybio Leverages Founders’ Experience, $145m In New Cash For Rare Diseases" - Scrip, 19 May, 2020.)and (Also see "Rallybio Looks To Deals To Grow ‘Transformative’ Rare Disease Pipeline" - Scrip, 2 Mar, 2022.)
Rallybio CEO Martin Mackay
Rallybio
The cumulative experience that Mackay and fellow Rallybio co-founders Stephen Uden, COO, and Jeff Fryer, bring to the table is impressive, as were their successes at Alexion. During their time there, the team helped develop some of the company’s most promising assets, and sell those to AstraZeneca PLC, paving the way for Alexion’s acquisition by the big pharma.
In an interview with In Vivo, Mackay reflected on his career, Rallybio’s growth strategy and what he has learned about leadership over the years.
Can you talk a bit about your history in the industry and what led you to co-found Rallybio?
I've only had one job all my life and that's been in pharmaceutical research and development. After leading R&D efforts at Pfizer and AstraZeneca, in 2013 I joined Alexion and that was really my first foray into rare diseases, which is now Rallybio’s focus. It was highly motivating to work in that space. We got to know patients, we got to know families and over a five-year period we brought forward some terrific medicines that are truly transformative for patients and their families.
In 2017, I announced my retirement, but I always had a hankering to see how I could run my own company. As it turned out, another person at Alexion– one of my co-founders, Steve Uden – was thinking exactly the same thing. I was very confident that we could develop good medicines, and we could hire great people and raise money. I felt good about all those components, but I was less convinced that the two of us could successfully run a business our first time. Fortunately, our third co-founder Jeff Fryer, who retired recently, had a strong business finance background, so the three of us launched the company in the beginning of 2018 around the notion of developing transformative therapies for patients with rare and devastating diseases.
When Steve Uden and I were thinking about a name for the company in 2017, Steve, who is a physician by training, was on his soapbox one day – and he is a very passionate gentleman – and he was saying, ‘What we need to do is rally the troops around the mission.’ He said this about three times and we looked at each other and instantly thought, that's a good name for a company. So, Steve takes 100% credit for ‘rally,’ I added the ‘bio,’ and that's how we got our name. It really is such a highly motivating area to work in.
I understand it is motivating to pursue therapies in rare disease areas, but it also makes good business sense.
It does. Alexion and other rare disease companies really showed that it is a thriving business, but absolutely key to the business side is coming up with medicines that really work. That sounds obvious, but we know there are lots of medicines on the market that might do a great job for some people but not for others, and many also have only incremental benefits to patients’ lives. What we set out to do with our lofty ambitions was to transform the life of the patient. We were able to do that in our former lives at Alexion, taking a patient from being deadly sick – for want of a better phrase – to being healthy again.
That said, we went into this with our eyes wide open that the pharmaceutical industry is challenging, and you have to come up with great medicines and that’s a long process with a lot of attrition. Fortunately, we have been able to attract really excellent investors, both as a private company and then, in August 2021, as a public company. The initial public raise of $90m and the follow-on raise of $55m gives us runway through to the beginning of 2025 that will allow us to hit the milestones that we've set out for ourselves.
Speaking of which, can you tell me what milestones you have reached and what is ahead for the business?
We have two really exciting lead programs and they both had very important milestones in the last year. The first program is for fetal and neonatal alloimmune thrombocytopenia, or FNAIT, which happens when there is a mismatch in HPA-1a between the mother and the fetus. During normal pregnancies, there are often bleeds from the fetus and the baby's platelets enter the maternal circulation by dint of these small bleeds. What happens when there is a mismatch is the mother’s immune system sees the platelets as being foreign, she raises antibodies and therefore alloimmunizes against these other platelets and, in turn, the antibodies cross back through the placenta and remove the platelets from the baby. This can lead to stillbirth, miscarriage, intracranial hemorrhage, severe neurological disabilities and thrombocytopenia. We know that around 2% of Caucasian women have the mutation that leads to this.
We acquired assets [a monoclonal HP1a antibody, now called RLYB-212] from a Norwegian company called Prophylix Pharma AS, after doing full diligence on this company. We really liked what we saw and we thought it was just the right type of program to bring into Rallybio because it ticked all the boxes: the biology was understood; the disease could lead to devastating consequences; and there's a very plausible treatment that we could bring to bear.
Why we’re excited about this program is we’ve established proof-of-concept in a Phase Ib study where we gave RLYB-212 to healthy males who were HPA-1a negative and then seven days later gave them a large dose of HPA-1a positive platelets. We showed very clearly that by giving the platelets even seven days later, there was enough medicine in the body to remove these platelets completely, which is exactly what we wanted to see. We are now doing a multidose trial and by the end of the year we'll know if we can give RLYB-212 to pregnant women and if it removes these platelets as quickly as we saw in males. In parallel, we will be doing a full maternal fetal toxicology program with the drug and that will readout by the end of this year.
We’re also doing a natural history study on FNAIT, which is really important for two reasons: we have great data on the Caucasian population, but while we know this mutation exists in other ethnicities, we don't know to what degree it exists. So, the first reason to do the natural history study is to find out what this looks like in other ethnicities. The second reason is to recruit investigators, recruit sites, work out the logistics of the diagnostics and prepare the ground for a clinical study.
Our second lead program is RLYB-116, which is a complement 5 inhibitor that we acquired from the SOBI organization [Swedish Orphan Biovitrum AB]. This is very different because we know this area very well as we spent time at Alexion working on complement inhibition and we came forward with some great medicines and great programs. Many of them are on the market now; it's a highly competitive space. In comparison, preventing FNAIT is a critical unmet need and we know of no competition. But we do think RLYB-116 has the potential to be best-in-class because it is a truly subcutaneous small volume complement inhibitor that rapidly, completely and in a sustained fashion reduces complement 5 from the bloodstream. The results we got back from our Phase I study at the end of last year, showed that with 100 milligrams in a 1 milliliter subcutaneous injection of RLYB-116, we could reduce C5 in volunteers by greater than 99%.
As to what indications we will go after with RLYB-116, there are the indications that are on the market, but there are also newer indications that we are quite compelled by. By the end of the year, we'll announce our indication strategy.
Since Rallybio is a portfolio company, what is your strategy for growing that asset portfolio?
It’s a combined approach. We have done two deals with truly excellent partners to add to our portfolio. One of the deals, which we did in 2021, was with Exscientia plc and that is for small molecule development. I've known the people in the company for over 25 years and they're really excellent scientists and have really worked out how to do medicinal chemistry in a modern way using AI and machine learning. We're running one program with them now called ENPP1, which is potentially for the treatment of hypophosphatasia, and that’s a multi-target deal. We also have others we’re working on with them but we've just not announced what those other targets are. So, if we have a small molecule target, we will work with Exscientia.
The other big deal, which we did last year, was with AbCellera Biologics Inc., and the thinking is very similar. They've got state of the art monoclonal antibody technology, so, if a target is amenable to antibody treatment, we will work with AbCellera. This is also a multi-target, multi-year deal.
Aside from that, we acquired an asset from Sanofi called matriptase-2 inhibitor [potentially for patients with severe anemia with ineffective erythropoiesis and iron overload, such as beta thalassemia and a subset of myelodysplastic syndromes, among others], which is now RLYB-331. Interestingly, it originally resided in a company called Kymab, which Sanofi bought as we were speaking to them about in-licensing matriptase-2. Once Kymab was bought, things went quiet for a little while, but we kept in dialogue with Sanofi and, long story short, we brought the asset in last year and we're very pleased about it. It was a great experience working with both Kymab and Sanofi to bring the asset in and it's in preclinical, so we're working on toxicology studies and in due course we'll take it into human testing.
We set very high hurdles in what we bring into the company, namely that it has to target a devastating rare disease; it has to have biology that we can put our hand on our heart and say that we understand what's going on; and it has to be a treatment that's going to be truly transformative. Because we set these really high hurdles, we've not done as many deals as maybe some folks have anticipated or maybe we anticipated, but the quality of the deals has been excellent.
What’s your five-to-10-year vision for the company?
We want to be a sustainable company, which means being a commercial-stage company. We're not in this for a quick flip, to bring in a few assets, develop them and then sell them off. We really want to take our assets all the way to the marketplace. We have a small commercial group now and we’re intent on building all our programs and we want the machinery to go all the way. We also recognize that partnering with bigger companies can be the best way to bring something to market and that can take various forms. As a public company we have to do our best for our shareholders and we're not against going into partnerships, but at the same time we want to be a sustainable commercial company and be the next favorite biotech that made it in this world.
As a venture capitalist yourself, what is your broader sense of what biotechs – which continue to have challenges finding investment dollars – can expect in the near-term?
My own perspective is that no matter what, great companies that have great assets that really address high unmet medical need will do well in any environment. I think VCs in general are keeping very close to the science, close to the action. They're still funding companies. I think what we are looking for is the more generalist investors to come back into the marketplace and biotech. They're understandably reviewing how they make their investments, but I do think the VC world will continue to be buoyant and great companies will continue to thrive.
Can you tell me about your leadership approach?
I’ve really tried to become a scholar of leadership and great leaders and what it’s fundamentally about is believing in the people that you work with, being close to them, treating them as human beings and doing so consistently through good times and bad times. I think what happens when you do that is people will be willing to work with you and stay with you and follow you.
Many of the people at Rallybio were at Alexion. I’ve known them for decades and we've worked together through that time, and I think that kind of consistency of being a decent human being has been fundamental to them making that switch. Of course, there are other aspects of successful leadership – you have to set a vision, you have to be realistic about what you're going to achieve, you have to work hard and be tenacious – and all these things are part of it, but I think treating people as human beings goes a long way.
Incidentally, I'm writing a book on leadership. I left school at 16-years-old in Scotland to work in a bacteriology laboratory in a hospital and I've had 31 bosses in my career. So, one of the themes in this book that I will eventually publish is what I’ve learned from working really closely with these people. Something I’ve found is that it’s not as simple as good leader/bad leader. They all had attributes that ticked some boxes, but not others, but you try and tick as many boxes as you can.
The last thing is that there is a need to produce stuff. You can be the nicest and most authentic person with high integrity, but you need to actually run the business. I'm very pleased with the medicines that we brought out of Pfizer and AstraZeneca and Alexion and are in the process of bringing out of Rallybio. I'm also really pleased to be working with such great people and be able to make an impact and have this deep motivation about continuing to do it right.
Also, becoming a grandfather re-energized me to try and do good with whatever small number of skills I have. Discovering medicines against rare diseases seems to be a decent place to do that.