Abcuro was founded based on the work of Steve Greenberg, a BWH clinician-scientist specializing in autoimmune diseases. Abcuro, initially focused on KLRG-1, an immune checkpoint target, which is expressed predominantly on CD8+ Tand NK cells.
Abcuro has two antibody programs, both at late preclinical stage, one for depletion of KLRG-1, and one for neutralization of KLRG-1, with promise in autoimmune disorders and immuno-oncology (IO), respectively. The company was financed in 2016, with the help of PIF, initially with a $2.25M seed round, and more recently extended with an $8M series A round. Steve comes to his medical insights through the study of human tissue, using microarrays and genomics to understand disease drivers and mechanisms. Steve starts with the patient, using bioinformatics to correlate human gene signatures with the severity of the disease to identify target candidates that are specific to that condition. An agent that selectively modulates that target is then a potential drug candidate.
His lab is small, but he punches above his weight because of his focus and access to clinically relevant samples. As an example of the power of this approach, Bristol-Myers Squibb had an anti-CTLA4 antibody that was not effective in the standard murine B-16 melanoma model, but despite that they decided to push forward into cancer trials, and it is now having a significantly positive impact for cancer patients.
Greenburg insists, “Always focus on the disease, start with clinical samples, don’t get stuck on a specific pathway, but look at global data in search of a single candidate that looks like the best target for that disease…”.
In addition to his clinical training, Steve studied mathematics at Princeton and then trained with Dr. Isaac Kohane, HMS chair of bioinformatics. His bioinformatic insights tackle disease from the opposite perspective of much of NIH funded research, starting with patients first. The venture bet with Abcuro is in part that this patient-focused approach is a more effective way to ameliorate human disease than the conventional manner starting with animal models of disease. For the IO program, Steve discovered the target from computational analysis of cancer tissue samples, and he found that it had been dismissed unfairly since the target was only relevant in humans was only relevant in humans while researchers were looking for it in traditional mouse models. For autoimmune disorders, Steve looked at direct patient sample data of inclusion body myositis patients from his labs at the Brigham.
Previously to Abcuro, Steve identified interferon-beta as an essential gene signature and an attractive target for dermatomyositis. He approached Pfizer to initiate a clinical trial, and that program is currently in phase 2 studies, jointly owned by Pfizer and BWH. Steve was intimately involved with the Pfizer drug development process, including attending weekly lab meetings, and from there he has a rich understanding of the discovery and drug development process. Similarly to Abcuro, Steve identified the gene signature with no animal models, and Pfizer bought into the human translational data. As that program continues, BWH will receive milestone payments, and if the drug ultimately succeeds, Steve will have significantly more funding to support scientific discovery in his lab.
Abcuro’s co-founder and CEO are Stefano Gulla; they met through the Pfizer collaboration (where Stefano was the project lead from Pfizer). The founding team has a diverse mix of skill sets – Stefano is very good at making biologics and Steve is a highly experienced clinician.
Abcuro also brought in Evan Thompson, who brings business and operations expertise acquired through a post-doc fellowship at MIT and subsequent employment at RA Capital. Steve’s lab continues to work on the biology related to KLRG-1 while Abcuro is focusing on developing therapeutics. “I still stay engaged with the company, I am chair of the scientific advisory board and very active in pursuing the science.” Recently, they added business executive Robert Millman and clinical immunologist Nalan Utku to the board, along with investors Jay Knowles from PIF and Yajun Xu from Shang Pharma. Steve, Stefano, and Evan brought their idea to PIF in 2016. PIF helped that competent team to recruit further investors, and to take a fledgling unfunded company through their seed and series A rounds. Abcuro was seeded in part with the help of Shang Pharma (SPI), who took on risk when Abcuro was little more than a theoretical target based on a literature search. SPI contributed “in-kind” resources through work done in their labs to generate antibodies in return for equity only. They helped recruit an additional Asian investor, to the syndicate led by PIF. Subsequently, the team raised an $8M series A round (which had more twists and turns than a Russian romance novel). This is a classic venture bootstrap story, and Steve hopes that it may encourage other scientists (both at NIH and in the industry) to generate drugs by focusing on patients first.