HotSpot Therapeutics Closes $100M Series C to Advance First-in-Class Allosteric Drug Discovery Platform to the Clinic

Boston, Mass., Nov 29, 2021 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of first-in-class allosteric therapies targeting regulatory sites on proteins referred to as “natural hotspots,” today announced the close of its oversubscribed $100 million Series C financing, bringing its total funding to $190 million.

Led by Pivotal bioVenture Partners, with significant participation by LSP and B Capital Group, the round includes new investors Monashee Investment Management, LLC, CaaS Capital Management, Revelation Partners and Pavilion Capital, as well as participation from previous investors, Atlas Venture, Sofinnova Partners, SR One Capital Management, funds managed by Tekla Capital Management, LLC, and MRL Ventures Fund. Ash Khanna, PhD, of Pivotal bioVenture Partners, and Fouad Azzam, PhD, of LSP, will join the HotSpot Board of Directors.

The new financing will be used to continue advancing HotSpot’s Smart AllosteryTM platform, with a focus on undrugged and poorly druggable targets, as well as the company’s existing pipeline.

“With the support of top-tier healthcare and technology investors, we will expand on the significant productivity of the Smart Allostery™ platform to enable a treasure trove of sought-after disease targets and thereby develop medicines that broadly benefit patients,” said Jonathan Montagu, Co-founder and Chief Executive Officer of HotSpot Therapeutics. “We have diligently established a deep pipeline of product opportunities in cancer and autoimmune disease, each offering a clear path to clinical value through precision and patient-targeted trial design.”

HotSpot’s Smart AllosteryTM platform unlocks a vast range of disease-relevant proteins for the first time through the identification of protein pockets called “natural hotspots.” Natural hotspots are pockets that are decisive in protein function yet previously unexploited using conventional allostery approaches. The Smart Allostery™ platform encompasses a broad suite of AI-enabled technologies and the industry’s largest and most diverse chemical library tailored to hotspots. The company is leveraging the Smart Allostery™ platform to uncover, capture, and drug natural hotspots across a wide array of disease-causing proteins.

“Within 36 months, HotSpot has established a new paradigm for allostery drug discovery that is reproducibly delivering small molecules across multiple target classes, including transcription factors and E3 ligases,” said Ash Khanna, PhD, Venture Partner at Pivotal bioVenture Partners. “We are thrilled to be partnering with HotSpot as they advance their pipeline to the clinic and realize the promise of delivering potentially lifesaving therapeutics to patients.”

Earlier this month, HotSpot announced new data validating its Smart AllosteryTM platform in the elucidation and preclinical evaluation of a novel allosteric inhibitor of the E3 ubiquitin ligase CBL-B, an important target in cancer immunotherapy. The data show successful targeting with the first and only selective small molecule inhibitors of CBL-B. Identified via the company’s Smart AllosteryTM platform, these small molecules promote T cell responses in vitro and in mice. Through allosteric inhibition of this negative regulator of immune cells, HotSpot’s small molecule CBL-B inhibitors offer the potential for increased immunotherapy efficacy for cancer patient populations that have historically exhibited poor treatment responses.


About HotSpot Therapeutics

HotSpot Therapeutics is targeting naturally occurring pockets on proteins called “natural hotspots” that are decisive in the control of cellular protein function. Largely unexploited by industry, these pockets are highly attractive for drug discovery and enable the systematic design of highly potent and selective small molecules that exhibit novel pharmacology. The company’s Smart Allostery™ technology platform utilizes AI-driven data mining of large and highly diverse data sets to identify pockets that matter on proteins, integrated with a tailored pharmacology toolkit and bespoke chemistry to rapidly deliver superior hotspot-targeted small molecules. The company has successfully exploited natural hotspots across multiple classes, including E3 ligases, kinases, and transcription factors. HotSpot has established a product pipeline of first-in-class small molecules for the treatment of cancer and autoimmune diseases, each enabled by precision and patient-targeted clinical design. To learn more, visit


Media Contact:
Darby Pearson
Verge Scientific Communications