Modifi Biosciences, Inc.

Merck & Co – known as MSD outside the US and Canada – has acquired Yale University oncology spinout Modifi Biosciences in a deal worth $1.3bn. The agreement gives Merck access to preclinical compounds designed to exploit DNA repair defects in difficult-to-treat cancers, including glioblastomas. Modifi, formed in 2021, has developed a new class of small molecules that target cancer cells lacking expression of a key DNA repair protein called MGMT. Approximately half of all glioblastomas and up to 80% of gliomas lack MGMT, which Modifi says makes these cancers a “natural first target” for its approach. Emerging research has also indicated that this MGMT deficiency is seen in many other tumour types. Merck has acquired all outstanding shares of Modifi for $30m upfront, with Modifi shareholders eligible to receive potential milestone payments totalling up to $1.3bn. David Weinstock, vice president, discovery oncology, Merck Research Laboratories, said: “DNA repair defects are a frequent hallmark of tumour cells and a major cause of resistance to cancer therapy. The… Modifi Biosciences team has developed an innovative approach that we believe has potential for treating some of the most refractory cancer types.” Also commenting on the deal, Modifi’s co-founder, Ranjit Bindra, said: “In founding Modifi Biosciences, we sought to radically change the oncology treatment paradigm for cancer patients with glioblastoma and other tumours. “We are honoured to have Merck recognise the potential of our science, and as an oncology company, [it is] perfectly positioned to advance our innovations through clinical trials and commercialisation.” Merck has made a number of acquisitions this year. In July, it completed its previously announced acquisition of EyeBio in a deal worth $3bn, giving it access to a late-stage candidate for diabetic macular oedema and neovascular age-related macular degeneration, as well as a preclinical pipeline targeting retinal diseases. The company also announced in April that it had acquired University at Buffalo laboratory spinout Abceutics in a deal worth $208m to improve antibody-drug conjugates safety, and acquired immuno-oncology company Harpoon Therapeutics and its pipeline of T-cell engagers for approximately $680m in March.

The technology developed by Modifi avoids traditional methods that indirectly target proteins in cancer cells. Credit: crystal light/Shutterstock. MSD has acquired US cancer therapeutics developer Modifi Biosciences, a Yale University spinout, enhancing its portfolio with preclinical compounds designed to target DNA repair defects in hard-to-treat cancers. MSD has acquired all outstanding shares of Modifi Biosciences through a subsidiary for an upfront payment of $30m. The deal also includes potential milestone payments of up to $1.3bn for Modifi’s shareholders. Modifi Biosciences co-founder Ranjit Bindra stated: “In founding Modifi Biosciences, we sought to radically change the oncology treatment paradigm for cancer patients with glioblastoma and other tumours. “We are honoured to have Merck recognise the potential of our science, and as an oncology company, they are perfectly positioned to advance our innovations through clinical trials and commercialisation.” The company’s research, initially published in Science [the peer-reviewed academic journal of the American Association for the Advancement of Science] in 2022, has shown preclinical data across various tumour models, including patient-derived xenograft glioma models. MSD research laboratories discovery oncology vice-president Dr David Weinstock stated: “DNA repair defects are a frequent hallmark of tumour cells and a major cause of resistance to cancer therapy. “The talented Modifi Biosciences team has developed an innovative approach that we believe has potential for treating some of the most refractory cancer types”. Modifi Biosciences co-founder Seth Herzon stated: “We designed our small molecules to have the ability to uniquely overcome clinical resistance mechanisms that have been known for decades but until now have been non-actionable. Additionally, we created the molecules in a manner which allows them to be rapidly progressed from bench to bedside.” The technology developed by Modifi Biosciences avoids traditional methods that indirectly target proteins in cancer cells. It demonstrated anti-tumour activity in laboratory research, inducing irreparable DNA modifications in cancer cells while sparing healthy tissue.

Modifi Biosciences, a spin out of Yale University founded in 2021, has been snapped up by Merck for $30 million paid upfront, and up to $1.3 billion in potential milestone payments. Modifi focuses on the development of small molecule drugs that target cancer cells with impaired DNA repair. “In founding Modifi Biosciences, we sought to radically change the oncology treatment paradigm for cancer patients with glioblastoma and other tumors,” said Ranjit Bindra, co-founder of Modifi Biosciences, professor of therapeutic radiology at Yale School of Medicine, and Scientific Director of the Yale Brain Tumor Center. “We are honored to have Merck recognize the potential of our science, and as an oncology company, they are perfectly positioned to advance our innovations through clinical trials and commercialization.” Modifi Biosciences has developed a new class of small molecule drugs that specifically target cancer cells that lack the expression of O6-methylguanine methyltransferase (MGMT), a protein that plays a key role in DNA repair. Mutations that affect DNA repair are common in cancer cells that can be exploited against them to treat drug-resistant forms of cancer. “DNA repair defects are a frequent hallmark of tumor cells and a major cause of resistance to cancer therapy,” said Dr. David Weinstock, vice president, discovery oncology, Merck Research Laboratories. “The talented Modifi Biosciences team has developed an innovative approach that we believe has potential for treating some of the most refractory cancer types.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); Research published by Modifi’s scientific founders in 2022 showed that this approach had promising results in mouse models of drug-resistant glioma, a type of cancer that affects the brain and spinal cord. Since then, the company has been conducting preclinical trials in models of glioma and glioblastoma; It is estimated that up to 80% of gliomas and approximately half of all glioblastomas lack the MGMT protein, making these types of cancer the ideal first target for Modifi’s new drug class. “We designed our small molecules to have the ability to uniquely overcome clinical resistance mechanisms that have been known for decades but until now have been non-actionable. Additionally, we created the molecules in a manner which allows them to be rapidly progressed from bench-to-bedside,” said Seth Herzon, co-founder of Modifi Biosciences and Professor of Chemistry at Yale.