CTLA-4/FasL fusion protein(KAHR Medical Ltd.)

Jerusalem’s KAHR Medical had been working on fusion proteins for autoimmune disorders for about 10 years, before “issues in development” spurred then-new CEO Yaron Pereg to change gears in 2017. “We had done our gap analysis and thought, ‘This is a very cool technology and very interesting platform, why won’t we start from scratch, do things different and also select more novel targets?’” he said. The company withdrew a Phase I/II application for its lead candidate, KAHR-102, before any patients were enrolled, and shifted to immuno-oncology. “Back then, you know, end of 2017, CD47 was not that attractive or as validated as it is today,” Pereg said. “Everybody went after adaptive immune cells — PD-1, PD-L1, CAR-Ts — and we thought the innate immune side of things could be very interesting.” On Wednesday, KAHR unveiled its second financing since the big pivot, raking in $46.5 million to advance its lead program, a CD47x41BB targeting fusion protein called DSP107. The company’s also setting some money aside to push two preclinical candidates — a TIGITxPD1 fusion protein and a LILRB2xSIRPa fusion protein — through IND-enabling studies. aMoon led the round, with some help from BVF Partners LP, DAFNA Capital Management LLC, Peregrine Ventures, Shavit Capital, the Cancer Focus Fund, Flerie Invest AB, Oriella Limited, Pavilion Capital, Hadasit Bio Holdings Ltd and Mirae Asset. KAHR’s candidates are designed to convert cancer’s camouflage into a beacon for the immune system to attack. Like other candidates in the space, DSP107 does so by binding to CD47 and blocking its infamous “don’t eat me signal.” Competition is stiff: Gilead’s $4.9 billion bet on Forty Seven last year appeared to trigger a wave of Big Pharmas joining the hunt for an effective CD47 drug, including AbbVie and Pfizer. Boehringer Ingelheim jumped on the bandwagon early, snagging the rights to a candidate from OSE Immunotherapeutics back in 2018. Gilead’s magrolimab snared fast track designation last September. And just a couple of months ago, Arch Oncology reeled in $105 million to fuel its CD47 mission. Where KAHR stands out, Pereg says, is that its fusion protein is bifunctional. It simultaneously binds to 41BB on T-cells. So while weakening the tumor’s defenses, it’s also designed to activate a natural and adaptive immune response, the CEO said. Upon completing the safety portion of the Phase I/II study “in the coming months,” Pereg plans to launch the candidate into two efficacy programs: One testing DSP107 as a monotherapy and in combination with Roche’s PD-L1 drug Tecentriq in advanced solid tumors; and another testing DSP107 alone and in combination with azacitidine or azacitidine plus venetoclax in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and T-cell lymphoproliferative diseases. Both the preclinical candidates should be ready for IND submission by the end of 2022, according to Pereg. “Cancer treatment is challenging in that cancer cells continuously change and develop resistance to existing treatments,” he said in a statement, adding that the company’s candidates could benefit patients who are non-responsive or refractory to existing immunotherapies.