Recurrent Lung Non-Squamous Non-Small Cell Carcinoma

Calithera Biosciences is expanding its oncology portfolio with the addition of two clinical-stage compounds from Takeda Pharmaceuticals. Both compounds, a Torc 1/2 inhibitor and a SYK inhibitor, have already shown promise in the clinic and have potential in biomarker-defined cancer patient populations. Late Monday afternoon, South San Francisco-based Calithera secured sapanisertib (CB-228, formerly TAK-228) and mivavotinib (CB-659, formerly TAK-659) to bolster its oncology pipeline. The company aims to initiate Phase II studies with both assets in 2022. Susan Molineaux, Ph.D., president and chief executive officer of Calithera Biosciences, said the company opted to secure the oncology assets because they believe the compounds will be an “excellent complement” to the company’s internally developed programs. Also, Molineaux said the compounds will be a good fit for Calithera’s strategic focus on biomarker-driven therapeutic approaches. Both Takeda assets have already demonstrated single-agent clinical activity. “We are encouraged by the promising single-agent clinical data that suggest these investigational therapies could help transform treatment for multiple cancer patient populations with high unmet need,” Molineaux said in a statement. Specifically, Molineaux said sapanisertib has the potential to become the first targeted treatment for patients who have NRF2-mutated squamous non-small cell lung cancer. Sapanisertib is a dual TORC 1/2 inhibitor that targets a key survival mechanism in KEAP1/NRF2-mutated tumor cells. She said Calithera has learned a significant amount regarding the unmet medical need of patients with KEAP1/NRF2 mutations. Molineaux said they learned how to identify and recruit these patients when Calithera previously conducted its KEAPSAKE trial evaluating telaglenastat in patients with stage IV non-squamous NSCLC with tumors that have a KEAP1 or NRF2 mutation. Molineaux said this latest approach to KEAP1/NRF2-mutant squamous NSCLC demonstrates the company’s commitment to those patients. The planned Phase II study will further evaluate sapanisertib as a monotherapy in patients with squamous NSCLC harboring a NRF2 mutation. Sapanisertib has already shown promising single-agent activity in patients with relapsed/refractory NRF2-mutated squamous non-small cell lung cancer. “Additionally, mivavotinib has the potential to be a best-in-class SYK inhibitor in non-Hodgkin’s lymphoma, as well as a first-to-market approach for patients with diffuse large B-cell lymphoma whose tumors harbor MyD88 and/or CD79 mutations,” Molineaux added. Mivavotinib is a SYK inhibitor that targets the constitutively active BCR pathway in many non-Hodgkin’s lymphoma cases. It also targets the “constitutively active inflammatory signaling pathway in MyD88-mutated NHL,” the company said. Calithera intends to begin a Phase II trial in squamous NSCLC with sapanisertib and a clinical trial in Diffuse large B-cell lymphoma (DLBCL) with mivavotinib. Both studies will be in biomarker-specific populations. In early clinical studies, mivavotinib showed promising single-agent responses in relapsed/refractory DLBCL. In addition, the company said recent preclinical studies have shown enhanced SYK activity and sensitivity to SYK inhibition in DLBCL and other NHLs harboring mutations in MyD88. Calithera anticipates data-defining clinical development and potential regulatory approval paths for both compounds could be generated within the next 12 to 18 months. Calithera acquired the assets for $10 million in upfront cash, as well as a $35 million stake in Calithera Series A preferred stock. Takeda will be eligible to receive clinical, regulatory, and sales milestone payments across both programs. The pharma giant will also be eligible for tiered royalties of high single-digits to low teens on future net sales should the assets be approved. Christopher Arendt, Ph.D., Takeda’s head of Oncology Cell Therapy and Therapeutic Area Unit, expressed confidence in Calithera’s capabilities to continue the development of sapanisertib and mivavotinib.

Jonathan Weiss/Shutterstock Eli Lilly will aim a checkpoint inhibitor it co-developed for the Chinese market at the United States and other western markets. Jonathan Weiss/Shutterstock Eli Lilly will aim a checkpoint inhibitor it co-developed for the Chinese market at the United States and other western markets. This morning, Eli Lilly and China-based Innovent Biologics expanded a strategic alliance involving TYVYT (sintilimab injection), an anti-PD-1 monoclonal antibody immuno-oncology medicine developed by the two companies for use in China. Lilly will pay Innovent $200 million in upfront monies to license the checkpoint inhibitor for the U.S. as well as other markets. TYVYT is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. The two companies began to market TYVYT in China in 2019 after the checkpoint inhibitor won approval in that company for relapsed or refractory classic Hodgkin’s lymphoma after at least two lines of systemic chemotherapy. TYVYT is the only PD-1 inhibitor to be included in China’s National Reimbursement Drug List. Anne White, president of Lilly Oncology, said through the expansion of the company’s collaboration with Innovent, Eli Lilly hopes to make TYVYT accessible to patients globally. “We believe TYVYT could deliver significant value to people living with cancer around the world and we intend to continue to study its potential across tumor types,” White said in a statement. Innovent Chief Executive Officer Michael Yu said the collaboration expansion with Eli Lilly marks the “first solid step in getting Innovent’s innovative portfolio into the global market.” Yu expressed confidence in the partnership with Eli Lilly due to that company’s commercial expertise. The two companies believe patients across the globe could benefit from treatment with TYVYT, Yu added. In addition to the $200 million in upfront money, Innovent will be eligible for up to $825 million in potential development and commercial milestones, as well as tiered double-digit royalties on net sales. Beyond Hodgkin’s lymphoma, the companies are also studying TYVYT as a potential therapy in non-squamous non-small cell lung cancer (NSCLC) and several other types of cancer. Earlier this month, the two companies released what they described as encouraging interim analysis data from the Phase III ORIENT-11 assessing TYVYT in combination with Alimta (pemetrexed for injection) and platinum chemotherapy as a first-line treatment for advanced or recurrent non-squamous NSCLC without sensitizing EGFR mutations or ALK rearrangements. Based on the interim analysis conducted by the Independent Data Monitoring Committee, the combination treatment demonstrated a statistically significant improvement in progression-free survival compared with placebo in combination with Alimta and platinum chemotherapy, which met the pre-defined efficacy criteria. A supplemental New Drug Application (sNDA) for this indication is under regulatory review in China. In addition, both companies will also retain the right to study TYVYT in combination with other medicines as part of their own clinical programs. hbspt.forms.create({ portalId: "4413123", formId: "c4dda430 - e2b0 - 4083 - 86f3 - ccce0c1d4479" });