NextPoint Therapeutics has announced an $80 million Series B funding round to move two lead precision immuno-oncology programs into the clinic. Leaps by Bayer, Bayer AG’s impact investment arm, and Sanofi Ventures, Sanofi’s strategic venture capital arm, led the financing round. Both programs of the Boston-based company use the recently discovered HHLA2 (HERV-H LTR-associating 2) pathway to turn on immune responses that fight tumors.

detlev biniszkiewicz
Detlev Biniszkiewicz, PhD, CEO of NextPoint Therapeutics, Managing Director at MPM, and Entrepreneur at BioImpact Capital, an affiliate manager of MPM.

“We discovered another checkpoint axis that is independently expressed from PD-1/L1 that nobody currently works on,” Detlev Biniszkiewicz, PhD, CEO of NextPoint, told GEN Edge.

“The hope is to develop something very similar to the successful PD-1 therapies. We have really strong IP around this axis, so part of the proceeds will be used to develop the research on this axis further. While we have an opportunity to develop our pipeline further, most of the proceeds will be used to bring two lead projects into the clinic.”

Some of the other new investors in this round are Sixty Degree Capital, Catalio Capital Management, Invus, and PagodaTree Partners. Along with NextPoint’s co-founder, Gordon Freeman, PhD, best known for discovering the PD-L1 and PD-L2 proteins, existing investors MPM Capital Management, Binney Street Capital, Dana-Farber Cancer Institute, and others participated in the financing. As a result of the financing, Paulina Hill, who is a Partner at Sanofi Ventures, and Rakhshita Dhar, who is the Senior Director of Venture Investments Health at Leaps by Bayer, will join the NextPoint Board of Directors.

A tale of two checkpoints

NextPoint is the brainchild of two scientific founders who independently discovered the HHLA2 pathway: alongside Freeman, of the Dana-Farber Cancer Institute, is Xingxing Zang, PhD, of Albert Einstein College of Medicine.

“In 2018, Gordon Freeman approached [MPM Capital Management] with this new and really exciting news,” said Biniszkiewicz. “After doing some research, we discovered that Xingxing Zang also independently discovered this novel pathway. We combined the work of both researchers into one company, which was really exciting because they are both leaders in the field.”

In both the gut and the lung, PD-1 is often found where tissue meets the lumen. “If you think about where the bacteria from the gut lumen interact with the lung, this is often where those molecules suppress immune activity,” said Biniszkiewicz. “The gut sees so much bacteria that if it were constantly inflamed, it wouldn’t function. Tumors learn to hijack this pathway to protect themselves, and we know that tumors upregulate PD-1 to protect themselves from the immune system.”

Most human tissues don’t have HHLA2, a ligand for receptor CD28H (TMIGD2 or IGPR1), but, according to Biniszkiewicz, immune cells in the placenta and intestines do. This is to help fetal-maternal immune tolerance or control inflammation in the intestines. Many human cancers overexpress HHLA, including cancers of the breast, lung, melanoma, pancreas, ovary, liver, colon, prostate, and esophagus.

“We discovered that HHLA2 is upregulated in an independent set of patients to protect against the immune system,” Biniszkiewicz said. “Similar to PD-1, we can select HHLA2-positive patients who are often PD-1-negative and drive monotherapy in these patients. So, the excitement is that [HHLA2] is another checkpoint, the closest we have seen to the PD-1/L1 pathway.”

MPM Capital Management invested slightly more than $2 million to seed NextPoint in 2020 and has been growing it since. “We have about 15-20 employees and intend to grow it further as we go into clinical development, making sure we have the right resources to push those projects into the clinic,” said Biniszkiewicz, who is a Managing Director at MPM and Entrepreneur at BioImpact Capital, an affiliate manager of MPM. He is also a board member of MPM’s portfolio company, iTeos Therapeutics (NASDAQ: ITOS).

“Almost 95% of current immuno-oncologists are focused on making PD-1 therapy better—we are not one of those companies,” said Biniszkiewicz. “I cannot tell you how unique it is to really work on patients that do not benefit from PD-1 therapy. I think that is really the key unmet medical need.”