By Richard Soll, Senior Vice President, WuXi AppTec (@richsollwx)
“Even though there has been a lot of work on the adaptive side, on the innate side, there’s much less being done, even though there are good reasons to think it will be – and we have pre-clinical data to support this – synergistic with other kinds of cancer therapies. I think that’s the reason the pharmaceutical industry is really interested in us right now because in oncology today combinations are very popular.”
Ten days after seasoned life science executive and venture capitalist Jonathan MacQuitty officially ‘retired” in January 2015, he was asked to help a biotech start-up that has a promising new approach on cancer by engaging the innate immune system. How could he say no? MacQuitty – who spent more than 30 years at VC firms such as Abingworth and with a handful of leading biotechs such as GenPharm, Genencor and Genentech – was up for the challenge.
MacQuitty and his team at Forty Seven, a clinical-stage immuno-oncology company, have secured $75 million in funding in a Series A round and have two Phase 1 clinical trials underway. The firm has also licensed the rights to over 100 patents and patent applications covering Hu5F9-G4, a humanized monoclonal antibody against CD47, and other immuno-oncology targets and antibodies from Stanford University.
Forty Seven is pioneering the advancement of immuno-oncology through the engagement of new and complementary phagocytic pathways that enhance anti-tumor efficacy and selectivity. I recently spoke with MacQuitty, who explained this unique approach, Forty Seven’s role in the immuno-oncology space, and how he likens the company to a fine wine.
Rich Soll: Forty Seven is focused on the immuno-oncology space, a hot area with lots of attention, deals and promise for the patients. How did you team up with the founders?
Jonathan MacQuitty: About a year ago, I retired after having spent over 15 years with Abingworth, a U.K-headquartered life sciences only venture capital group. I was traveling and doing some board work and consulting, and some teaching, and then it was suggested that I get together with Forty Seven’s founders. At that time, they hadn’t formulated the details of how to build and finance a new company, but they had done an enormous amount of work on the technology. I was asked to help with formulating plans. I made some suggestions and spent some time with them, and after a few months I ended up being CEO.
Rich Soll: How did the founders of Forty Seven convince you to become the CEO after retiring, and how have you ramped up the company so far?
Jonathan MacQuitty: I don’t know how much you know about this technology, but it’s really incredibly powerful stuff. This was a once in 20-to-30 year opportunity, so I was delighted to get involved. In the last 12 months, we have pulled together a powerful syndicate. We now have four VCs, and have raised $75 million. We have licensed over 120 patent applications and patents. We have a full management team, 12 initial employees, two Phase 1 clinical studies, and enormous interest from the pharmaceutical industry. Even when we were in stealth mode, several pharma companies wanted to collaborate with us, and indeed there are some potent reasons for them to want to do that. For the first six-to-nine months we operated essentially from the living room of my house. Later this year we will be moving in to a sizable lab and office facility.
Rich Soll: So, tell me about the name of the company. Does it have a special meaning?
Jonathan MacQuitty: Yes, if we have any Bordeaux drinkers out there, they will know that 1947 was a stunningly good vintage. We have several board members who like Bordeaux, so that is sort of a hidden fact. But, of course, it’s really named after CD47, the main target our team is focused on. We thought it was a distinctive name that people would remember, and so far I’d say that the name is working well.
Rich Soll: Let’s talk about the science some more. Can you explain how CD47 is a different approach from other therapeutics in this space?
Jonathan MacQuitty: Essentially there are two different arms to the immune system that operate in parallel. One is called the adaptive arm that’s modulated mainly by T-cells and B-cells. If you look at the immuno-oncology field to date, it’s mostly been focused on the adaptive immune system. But we have another parallel arm called the innate immune system which is modulated mainly by white blood cells called macrophages. They act a bit like Pac-Man by engulfing and digesting bad cells through a process called phagocytosis. Even though there has been a lot of work on the adaptive side, on the innate side much less has been done, and the Stanford team is clearly in the lead. Therapies focused on the innate immune system appear synergistic with other kinds of cancer therapies, and we have pre-clinical data to support that. I think that’s the reason the pharmaceutical industry is really interested in the company because synergistic combinations are very popular right now in oncology. So we could have a combination in which two entirely different arms of the immune system get activated simultaneously to go after the cancer.
CD47 is a ‘don’t eat me’ signal that is present on human cells primarily to let macrophages know not to eat them up. Cancers up-regulate CD47 on their surface to avoid the process of macrophages attacking them. The Stanford team created a way to mask the CD47 signal so when macrophages comes along they can eat up the cancer cells.
Rich Soll: Many cells express this protein; so how selective is the mask?
Jonathan MacQuitty: Here are some of the subtleties: Bad cells generally have ‘eat me’ signals so it’s a balance of ‘eat me’ and ‘don’t eat me’ signals. We have preclinical and some clinical data to say it’s selective. There is one exception to that – old red blood cells are cleared from the blood system via phagocytosis through ‘eat me’ signals. In fact, if you mask the ‘don’t eat me signals’ on the red blood cells, they will be eaten up at an earlier age. With this therapy there is a one-time resetting of the population of red bloods cells (a slight anemia) and after that, there seems to be no further issue.
Rich Soll: Immunotherapy is such the rage right now, but it has some current limitations. What are your thoughts on that?
Jonathan MacQuitty: Well the good news is that for a subset of patients (responders), they do seen to get long duration of benefits from the treatment. We’ll see if that continues to be the case, but certainly it seems to be so far. If you look at survival, you could have patients who remain cancer free for many years later. This is very different from what you would get from a cytotoxic agent. The immune system seems to continue to keep the cancer in check for these responders. Now, the bad news is it doesn’t work on all patients – the non-responders – and the side effect profile is not innocuous. But people are willing to have some tradeoffs with these treatments due to these very impressive responses.
Rich Soll: Would you expect a similar kind of limitation for CD47?
Jonathan MacQuitty: We don’t know the answer to that yet. We don’t know yet how broad the impact is going to be, but I would say that the pre-clinical work in vivo and in vitro is impressive. So what cancers will this not work on? We don’t know, but we have not thought of any cancers where we know for sure that this treatment wouldn’t work.
Rich Soll: So you are already in the clinic. Can you give us an update?
Jonathan MacQuitty: We have over 20 patients enrolled, we have a solid tumor study and an acute myeloid leukemia underway, so we have two different Phase 1’s up and running. They will finish later this year.
Rich Soll: Have you started looking at combination therapies yet?
Jonathan MacQuitty: Pre-clinically, yes. The data looks really good, with antigen-specific antibodies and with other kinds of combinations. A year from now we will be able to talk more about that. But the pre-clinical data certainly looks interesting so far.
Rich Soll: Are you looking at any other developments in the company?
Jonathan MacQuitty: We hope to be starting two additional studies by the end of the year, but we have not announced what they will be. And we also have additional pre-clinical compounds which are working their way toward an IND filing.
Rich Soll: Is there much competition in this area?
Jonathan MacQuitty: Not a huge amount. Celgene has an antibody in a clinical trial which started last year. But if you compare this to very large numbers of PD-1’s and PD-L1’s in clinical trials, there is a lot less competitive activity.
Rich Soll: Forty Seven was able to raise $75 million this year. Is raising money harder to do for biotechs these days?
Jonathan MacQuitty: Getting an investment isn’t quite as easy as it used to be, but I always think there is room for something truly exceptional. The public markets are also less attracted to biotech currently, but I think there are still plenty of good ideas around. For Forty Seven, we are fortunate to have both a strong management team and solid investment support, which will enable us to fully explore the clinical effectiveness of our lead molecule and other parts of our licensed technology. Our patent portfolio also has broad potential applications outside of cancer, which is also attractive to investors. So it’s going to be a very exciting and busy the next few years for us.