NCX1

Patrick Seeger/picture alliance via Getty Four years after partnering with GammaDelta Therapeutics to develop therapies for solid tumors, Takeda pulled the trigger and exercised its option to acquire the London-based company. The deal was struck one month after GammaDelta dosed its first patient in a Phase I acute myeloid leukemia (AML) trial. The deal brings GammaDelta’s allogeneic variable delta 1 (Vδ1) gamma-delta (γδ) T cell therapy platforms under its umbrella. The GammaDelta platform includes blood-derived and tissue-derived platforms, as well as early-stage cell therapy programs. Among the assets included in the deal is GammaDelta’s experimental AML drug, GDX012, an allogeneic, non-engineered, variable delta 1 gamma-delta T cell therapy manufactured from healthy donor blood. The primary objectives of the Phase I study are to assess the safety, tolerability, pharmacokinetics, anti-leukemic activity and maximum tolerated dose of GDX012 Christopher Arendt, Ph.D., Takeda’s head of oncology cell therapy and therapeutic area unit, expressed his excitement about the potential impact the GammaDelta platform could have on patients. “Gamma-delta T cell-based therapies represent a differentiated approach to target both solid tumors and hematological malignancies, and we are eager to integrate GammaDelta’s cell therapy platforms into our immuno-oncology R&D efforts,” Arendt said in a statement. He said the deal for GammaDelta allows the company to broaden its immunotherapy offerings through the mechanisms of potential treatments that leverage innate immune responses. Those types of responses serve as the body’s first defense mechanism against diseases and include multiple mechanisms, including γδ T cells and natural killer cells. According to company data, Vδ1 γδ T cells are a unique subset of T cells that specifically recognize and are activated by molecular patterns of dysregulation on cancer cells. The GammaDelta platform has led to the development of allogeneic cell therapies that are highly active preclinically against solid tumors and hematological malignancies, the company said. Takeda and GammaDelta first collaborated in 2017 in a $100 million pact. For Takeda, that partnership included an equity stake in GammaDelta, as well as an option to acquire the company. Terms of the acquisition were not disclosed in the announcement. However, Takeda noted that the deal includes a pre-negotiated upfront and future potential milestone payments, subject to certain adjustments. Paolo Paoletti, chief executive officer of GammaDelta, called the acquisition decision the “culmination of years of a fruitful collaborative partnership.” Paoletti said the acquisition recognizes his company’s promising progress in developing novel technologies to treat solid and blood-based tumors. “Through our work together, we’ve made great strides in developing our proprietary γδ T cell therapy platforms, which have enabled the development of a pipeline of innovative cell therapies and allowed for the advancement of our first program into Phase I clinical development,” Paoletti said in a statement. “This acquisition builds on the tremendous work of our talented team and provides the foundations to enable rapid development of a portfolio of innovative allogeneic cell therapies, focused on improving outcomes for patients with cancer.” GammaDelta isn’t the only company with whom Takeda forged a relationship in 2017 and then went on to acquire. Earlier this year, the Japanese pharma giant snapped up partner Maverick Therapeutics in a deal valued at up to $525 million. The lead asset from that partnership, TAK-186 (formerly known as MVC-101), is a first-in-class active T-cell engager. It is being assessed in a Phase I/II trial for the treatment of EGFR-expressing solid tumors For Takeda, the acquisition of GammaDelta comes shortly after the company divested a Torc 1/2 inhibitor and an SYK inhibitor to Calithera Biosciences. Arendt expressed confidence in that company’s capabilities to continue the development of sapanisertib and mivavotinib. Featured Jobs on BioSpace

Calithera started the year by axing a third of its staff after a monumental Phase II flop in renal cell carcinoma. And while CEO Susan Molineaux has refused to give up on the program, she’s going to need an assist if she wants to close the year on a higher note. That’s where Takeda comes in. For two upfront payments of $10 million and $35 million, tiered royalties and an undisclosed amount in biobucks, Takeda is forking over two Phase II-ready cancer programs to Calithera — one of which targets KEAP1/NRF2 mutations, the same ones Calithera is now pursuing with its once-failed glutaminase inhibitor telaglenastat. “We have learned a great deal about the unmet medical need of patients with KEAP1/NRF2 mutations, as well as how to identify and recruit these patients, during the conduct of our KEAPSAKE trial evaluating telaglenastat,” Molineaux said in a statement. “This complementary approach in KEAP1/NRF2-mutant squamous NSCLC demonstrates our commitment to these patients and the pathway.” The first new candidate in Calithera’s basket is Takeda’s dual TORC 1/2 inhibitor sapanisertib. It’s designed to target a key survival mechanism in KEAP1/NRF2-mutated tumor cells, which are found in a considerable amount of patients with solid tumors, according to the companies. If all goes according to plan, the program is heading into a Phase II trial early next year as a monotherapy in patients with squamous NSCLC harboring a NRF2 mutation, with a readout coming in the next 12 to 18 months. The South San Francisco-based biotech is also getting mivavotinib, an SYK inhibitor that’s also expected to enter Phase II next year for patients with diffuse large B-cell lymphoma with and without MyD88 and CD79 mutations. Calithera also sees potential for studies in non-Hodgkin’s lymphoma and blood cancer. That makes five clinical programs now in Calithera’s pipeline, according to the company’s website. Calithera is still reeling from its Phase II failure in renal cell carcinoma, the results of which were read out back in January. Adding telaglenastat to Exelixis’ Cabometyx failed to improve progression-free survival, investigators concluded. In fact, patients on Cabometyx and placebo lived slightly longer — a PFS of 9.3 months compared to 9.2 months for those treated with telaglenastat and Cabometyx, which doesn’t mean much considering the hazard ratio of 0.94 was far off statistical significance (p=0.65). The company’s stock $CALA is still trading at less than half of what it was last December. Shares were up 1% in premarket trading on Tuesday, going for $2.03 apiece. While that was the end of the road for telaglenastat’s Phase II study in renal cell carcinoma, Molineaux is pushing forward with another Phase II study in KEAP1/NRF2 mutant NSCLC patients, dubbed KEAPSAKE, which dosed the first patients last summer.

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.