Simcha Therapeutics Accelerates Growth with Key Leadership Appointments, Expanded Research and Option Agreement with Yale School of Medicine

Company Appoints Accomplished Biotech Leaders Sanuj Ravindran, M.D., as Chief Executive Officer and Jake Bauer as Independent Director and Chair

NEW HAVEN, Conn., and SOUTH SAN FRANCISCO, Calif. – August 16, 2022 – Simcha Therapeutics (“Simcha”), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, today announced the appointment of Sanuj Ravindran, M.D., as chief executive officer and director, and Jake Bauer as an independent member and chair of its board of directors.

Simcha has also expanded its sponsored research agreement with Yale School of Medicine related to cytokine biology in the laboratory of Aaron Ring, Ph.D., M.D., associate professor of immunobiology and Simcha founder. Through this expanded agreement, the company will support research in the Ring Laboratory focused on overcoming biological limitations of native cytokines. Simcha holds an exclusive option to license multiple therapeutic agents resulting from the expanded research agreement.

“With the support of our successful Series B financing and encouraging progress being made with ST-067 in the clinic, Simcha is entering a stage of dynamic growth with even greater opportunity ahead,” said Bauer. “I’m thrilled to have joined the company earlier this year, and excited to have recruited Sanuj, a skilled and thoughtful leader, to guide Simcha as it navigates its many potential avenues for growth.”

Dr. Ravindran remarked, “Simcha is built on a remarkable scientific foundation and Aaron’s bold vision that patients deserve more than incremental advances. Together these have led to the advancement of a promising first-in-class therapeutic in ST-067, our decoy resistant IL-18 agent; and created a new way forward for IL-18 as a potentially powerful and broadly applicable cancer immunotherapy pathway. As Simcha continues to explore the breadth of ST-067’s potential in the clinic, and as we accelerate the advancement of other engineered cytokines, I feel privileged to build and lead a patient and product focused organization with a commitment to pioneering truly transformational therapies.”

Dr. Ravindran has spent more than 20 years in strategic and operational roles across the life science industry, both as an investor and company builder. Most recently, he served as CEO-in-residence at BridgeBio (BBIO) where he was chief executive officer of PellePharm and executive chair of Phoenix Tissue Repair. In these roles, Dr. Ravindran led the companies’ growth, directed strategy, secured significant partnerships, and advanced pipeline programs in oncology and rare skin diseases through mid- and late-stage clinical trials. Before this, he served as chief business officer at aTyr Pharma (LIFE), a clinical-stage protein therapeutics company focused on tRNA synthetases. Prior to that, Dr. Ravindran was senior vice president of corporate development at The Medicines Company (MDCO), where he led multiple transactions totaling more than $2 billion in potential value. He began his biotech career as a venture capitalist for 10 years with Burrill & Company, Radius Ventures, and Asian Healthcare Fund. Dr. Ravindran was previously a practicing physician, board-certified in Internal Medicine, having completed his residency training at Thomas Jefferson University Hospital. He received his bachelor’s degree from Northwestern University, his doctorate in medicine from Jefferson Medical College, and his master’s of business administration from the Kellogg School of Management.

Dr. Ravindran joins Beatrice McQueen, Ph.D., on the Simcha leadership team, who was recently appointed chief operating officer and has led Simcha’s finance and operations since its inception.  Dr. McQueen has spent over 20 years in various operational roles, working to advance programs at leading organizations such as Amgen, PPD and Pfizer.

Bauer, having previously served as chief business officer of MyoKardia, is currently a venture partner with ARCH Venture Partners and SR One Capital Management. He and Dr. Ravindran join the Simcha board of directors with existing members Simeon George, M.D., CEO of SR One; Sean Li, Ph.D., of WuXi AppTec; Terry Rosen, Ph.D., CEO of Arcus Biosciences; and Aaron Ring, M.D., Ph.D., founder of Simcha Therapeutics.

About Simcha Therapeutics

Simcha Therapeutics is a clinical-stage immunobiology company pioneering the development of first-in-class engineered cytokine therapeutics with transformational promise for patients. The company is built on a foundation of scientific rigor to overcome biological challenges in clinically translatable pathways, exemplified by the first decoy-resistant interleukin-18 (IL-18). By unlocking the potential of IL-18, Simcha is developing its lead program (ST-067) as monotherapy and in combination with potentially several other anticancer agents.  ST-067 is currently being studied in a Phase 1/2 clinical trial, in patients with solid tumors and who have progressed on other immunotherapeutic agents. Beyond IL-18, the company’s underlying approach to immune-biology and cytokine engineering has broader potential to support disease-modifying therapeutic options for a range of significant diseases.  For more information, please visit

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Simcha Therapeutics Raises $40 Million Series B Financing and Initiates Phase 1/2 Study to Evaluate Novel Interleukin-18 Variant in Cancer

Financing led by SR One; Proceeds to advance proprietary IL-18 variant through Phase 2 clinical trial ST-067 is a first-in-class “decoy resistant” IL-18 variant designed to overcome IL-18 binding in the tumor microenvironment

NEW HAVEN, Conn., Jan. 27, 2022 (GLOBE NEWSWIRE) — Simcha Therapeutics, a biotechnology company developing cytokine-based cancer immunotherapies, today announced the closing of a $40 million Series B financing. The round was led by SR One Capital Management and joined by other new investors including BVF Partners, Samsara BioCapital, Rock Springs Capital, ArrowMark Partners, and Logos Capital. In conjunction with the financing, Simeon George, MD, Chief Executive Officer of SR One Capital Management, has joined the Simcha Therapeutics Board of Directors.

In addition, the Company has dosed the first patient in the Phase 1 portion of a first-in human multi-center Phase 1/2 clinical trial of its first drug candidate ST-067, a first-in-class “decoy-resistant” Interleukin-18 variant. The study is designed to evaluate the safety and bioactivity of ST-067 in a broad set of solid tumor types.

“We intend to become a leader in creating the next-generation of cytokine immunotherapies, and this investment from a phenomenal group of blue-chip firms represents a major endorsement of our progress to date and future potential,” said Aaron Ring, MD, PhD, Simcha Therapeutics Founder and Assistant Professor of Immunobiology at the Yale School of Medicine. “The Series B comes at a pivotal time in Simcha’s development as we have transitioned to a clinical-stage company and continue to build our leadership team.”

Dr. George added, “Simcha is developing highly innovative drugs that are completely unlike any other immunotherapeutic agent in development. We are proud to support the company in advancing this extremely promising agent for cancer patients.”

About Simcha Therapeutics

Simcha Therapeutics uses directed evolution to engineer novel cytokines designed to unlock the precision and power of the immune system. Simcha’s lead program, ST-067, is a designer IL-18 cytokine that has shown potent antitumor effects in animal models, both as a monotherapy and when combined with anti-PD-1 checkpoint inhibitors, as described in Nature in June 2020. A Phase 1 clinical trial commenced in the second half of 2021. Simcha was founded in 2018 by Aaron Ring, MD, PhD, Assistant Professor of Immunobiology at the Yale School of Medicine.

Simcha Therapeutics Launches to Engineer Therapeutic Cytokines to Unlock the Full Potential of the Immune System

Scientific paper in Nature describes use of directed evolution to develop Simcha’s lead program, a customized IL-18 cytokine with potent antitumor efficacy

$25 million Series A financing will take lead asset into clinical trials early next year

NEW HAVEN, Conn.–(BUSINESS WIRE)–Simcha Therapeutics, a biotechnology company developing first-in-class biologic drugs that modulate powerful cytokine pathways, launched today with $25 million in Series A financing and a mission to harness the precision and power of the immune system through the use of directed evolution.

Simcha’s lead program involves a customized variant of interleukin-18 (IL-18), a cytokine with potent antitumor effects, developed in the lab of Scientific Founder Aaron Ring, M.D., Ph.D., Assistant Professor of Immunobiology at the Yale School of Medicine. The biology and preclinical profile of this molecule, which Simcha expects to advance to the clinic in the first half of 2021, is described in detail in a scientific paper published today in the journal Nature.

Cytokine therapies heralded the immuno-oncology revolution more than 30 years ago with the discovery that interleukin-2 (IL-2) could promote rare, but dramatic, responses in melanoma and kidney cancer patients. However, they have not lived up to their promise as a class due to substantial toxicities and limited efficacy. Simcha was founded to overcome those obstacles by using directed evolution to engineer a new generation of cytokines with improved properties relative to those of their native variants. Simcha’s molecules are purpose-built to control immune cell activation, differentiation and proliferation — and to reverse the immunosuppressive tumor microenvironment that is a barrier to effective eradication of the cancer.

“Cytokines represent a compelling therapeutic class because they tap into pathways that are hard-wired into immune cells. The challenge is that nature didn’t design them to be anti-cancer therapies; they’re signaling molecules, so their activity can be hard to specifically direct,” Dr. Ring said. “At Simcha, we set out to improve on nature’s design by engineering custom-built proteins that can precisely activate and expand populations of crucial immune responders, such as natural killer (NK) cells and T cells. Too many cancer patients do not respond to the immunotherapies available today. We’re hopeful that our approach will provide new options and potential benefits to these patients.”

Evading a “Decoy” Receptor

Simcha’s lead asset, ST-067, activates the IL-18 receptor, triggering potent inflammatory signaling in antitumor immune cells of both the adaptive and innate branches of the immune system.

Early efforts by leading pharmaceutical companies to develop IL-18 into a drug failed. Dr. Ring’s lab broke new ground by identifying the reason for that failure: The tumor microenvironment is teeming with a “decoy” called IL-18BP, which binds IL-18 and blocks it from activating its receptor. When infused as a drug, IL-18 is drawn to the decoy and fails to reach its true target. As described in the Nature paper, the decoy receptor is a “major barrier to IL-18 immunotherapy.”

To overcome that barrier, Dr. Ring’s lab used directed evolution to create a version of the cytokine that would evade the decoy and bind only to the true IL-18 receptor. This was a difficult task, since IL-18 normally binds its decoy 10,000 times tighter than it does to the IL-18 receptor. The designer version of IL-18 made in Ring’s lab has dramatic alterations in its receptor binding properties, biasing binding towards the IL-18 receptor and away from the decoy by more than one million-fold. This “decoy-resistant” property enables the custom-built cytokine to work effectively in the immunosuppressive tumor microenvironment.

Potent Single-agent Antitumor Effects

When Ring’s lab tested the decoy-resistant IL-18 and compared it to natural IL-18 in mice, they found that — just as in human patients — natural IL-18 had little to no antitumor activity. By contrast, the decoy-resistant IL-18 had potent single-agent activity that inhibited tumor growth and even produced complete tumor regression in many animals, including in tumor types that are refractory to checkpoint inhibitors.

Ring’s lab also examined the effect of decoy-resistant IL-18 on the tumor microenvironment. A key finding: The engineered IL-18 acted on a crucial population of “stem-like” T cells within tumors, increasing their numbers over tenfold and skewing their development toward a highly active effector phenotype, as opposed to an exhausted or dysfunctional state. In checkpoint-resistant tumors, the engineered IL-18 also acted on innate NK cells, increasing their numbers and maturation to promote antitumor activity.

“The mechanism of action of decoy-resistant IL-18 is unique and distinct from immunotherapeutic agents that are being developed for other pathways. For this reason, we are hopeful it could be effective in tumors that have not otherwise responded to immune-based treatments, as well as enhance the activity of standard cancer immunotherapies,” said Dr. Ring.

Founder’s Strong Record in IO Drug Discovery

Dr. Ring has a strong track record in immuno-oncology drug discovery. He co-invented the first described CD122-biased IL-2 variant, originally detailed in Nature in 2012, which is now advancing through preclinical studies at Medicenna Therapeutics. He also developed a high-affinity SIRPα antagonist, featured in Science in 2013, that is now in clinical development at ALX Oncology as ALX-148. For these and other discoveries, Ring was named to Forbes ‘30 under 30’ list of rising stars in health care in 2016 and has been honored with an NIH Director’s Early Independence Award and recognition as a Pew-Stewart Scholar in Cancer Research.

Simcha plans to build out a full executive team as the company prepares to move ST-067 into the clinic next year.

The company’s investors include WuXi AppTec’s Corporate Venture Fund, Sequoia Capital China and Connecticut Innovations.

About Simcha Therapeutics

Simcha Therapeutics uses directed evolution to engineer novel cytokines designed to unlock the precision and power of the immune system. Simcha’s lead program, ST-067, is a designer IL-18 cytokine that has shown potent antitumor effects in animal models, both as a monotherapy and when combined with anti-PD-1 checkpoint inhibitors, as described in Nature in June 2020. A Phase 1 trial is expected to be launched in the first half of 2021. Simcha was founded by Aaron Ring, M.D., Ph.D., Assistant Professor of Immunobiology at the Yale School of Medicine. The company has received $25 million in funding to date and is based in New Haven, Conn.