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Curis Doses First Patient in Phase 1 Study of CA-4948 in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes

On July 7, 2020 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that the first patient has been dosed in its Phase 1 trial evaluating CA-4948, a novel, small molecule IRAK4 kinase inhibitor, in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) with spliceosome mutations, such as SF3B1 and U2AF1, that drive expression of the long isoform of IRAK4 (IRAK4-L) (Press release, Curis, JUL 7, 2020, View Source [SID1234561717]). IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, and these pathways are frequently dysregulated in patients with AML and MDS.

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"When Drs. Daniel Starczynowski, Professor, Cincinnati Children’s Hospital and Amit Verma, Director of the Division of Hematologic Malignancies at the Albert Einstein College of Medicine, demonstrated the important pathogenic role of IRAK4 in MDS/AML in their seminal publication in Nature Cell Biology and presentation at ASH (Free ASH Whitepaper) last December, everyone in the AML/MDS community paid attention, including our team at Curis," said James Dentzer, President and Chief Executive Officer of Curis. "Dr. Starczynowski, Dr. Verma, and their colleagues showed that IRAK4-L, the oncogenic long isoform of IRAK-4, is expressed as a result of specific spliceosome mutations common in AML and MDS. Further, they demonstrated that it potentially impacts over 50% of the AML/MDS population. We quickly worked with our clinical investigators and the U.S. Food and Drug Administration (FDA) to design a study of CA-4948, our first-in-class IRAK4 inhibitor, in this population. We are pleased to announce today, just six months later, that we have initiated this new study and successfully dosed our first patient. The initial dose in this study is 200mg twice-daily (BID) which, based on our preclinical models, we believe may be a therapeutic dose level. As a result, we expect to report initial efficacy data by the end of the year."

"Historically, no single oncogenic driver of AML and MDS has been known to impact the majority of patients," said Dr. Guillermo Garcia-Manero, Chief, Section of Myelodysplastic Syndromes at the University of Texas MD Anderson Cancer Center. "Recent studies have changed this understanding. The long isoform of IRAK4, itself the result of specific genetic mutations, was recently discovered to be a driver of disease in over half the population of patients with AML and MDS. With CA-4948, we may now have a single drug that can directly target a key driver of disease in these patients. We are delighted to be a lead clinical site in the study of this novel new drug."

About the CA-4948 Phase 1 Clinical Trial

The Phase 1 trial is an open-label, dose escalation study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of CA-4948 in patients with AML and high-risk MDS. The primary objective of the study is to determine the maximum tolerated dose and recommended Phase 2 dose of CA-4948 based on safety and tolerability, dose-limiting toxicities (DLTs), and pharmacokinetic and pharmacodynamic findings. A minimum of three patients will be enrolled at each dose level, starting with 200 mg BID, which was determined to be safe, capable of achieving relevant levels of drug exposure, and demonstrated signs of biologic activity and clinical efficacy in a separate, ongoing Phase 1 study. Each treatment cycle will be 28 days in length and repeated in the absence of toxicity. Initial data from the study is expected in the fourth quarter of 2020.

TURNING POINT THERAPEUTICS AND ZAI LAB ANNOUNCE EXCLUSIVE LICENSE AGREEMENT FOR REPOTRECTINIB IN GREATER CHINA

On July 7, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, and Zai Lab (NASDAQ: ZLAB), an innovative commercial-stage biopharmaceutical company, reported an exclusive license agreement for the development and commercialization of Turning Point’s lead drug candidate, repotrectinib, in Greater China, which includes mainland China, Hong Kong, Macau and Taiwan (Press release, Zai Laboratory, JUL 7, 2020, View Source [SID1234561716]).

Under the terms of the agreement, Zai Lab will obtain exclusive rights to develop and commercialize repotrectinib in Greater China and Turning Point Therapeutics will receive a $25 million upfront payment, with potential to receive up to an additional $151 million in development, regulatory and sales-based milestone payments. Turning Point will also be eligible to receive mid-to-high teen royalties based on annual net sales of repotrectinib in Greater China.

"With more than 700,000 newly diagnosed lung cancer patients every year in Greater China, and the development and commercialization capabilities Zai Lab have shown over time in the region, we view Zai Lab as the ideal partner to help expand the potential reach of repotrectinib," said Athena Countouriotis, M.D., President and Chief Executive Officer of Turning Point Therapeutics. "Our collaboration with Zai Lab is a strategic step to potentially accelerate the development of repotrectinib in Greater China."

Zai Lab anticipates opening additional sites for the TRIDENT-1 Phase 2 registrational clinical study of repotrectinib. The ongoing study is currently active in 11 countries globally and enrolling patients with ROS1-positive advanced non-small cell lung cancer (NSCLC) and NTRK-positive solid tumors.

"We are very pleased to enter into this agreement with Turning Point Therapeutics. Repotrectinib is highly synergistic with Zai’s existing pipeline and further strengthens our disease area strongholds across most common tumor types in China, particularly in lung cancer. We are looking forward to bringing this potential best-in-class agent in the front-line setting and for patients previously treated with an tyrosine kinase inhibitor (TKI) where there are no approved targeted therapies," said Samantha Du, Ph.D., Founder, Chairwoman and Chief Executive Officer of Zai Lab.

"In China, there is only one approved targeted therapy for patients with advanced ROS1-positive lung cancer and despite its efficacy, most patients eventually acquire resistance," said Dr. Lu Shun, Director of Chinese Lung Cancer Association. "The unmet need in the ROS1-positive lung cancer patient population is significant. The preliminary clinical activity and safety data generated to date for repotrectinib represent a promising clinical profile. If approved, repotrectinib has the potential to be the standard of care for ROS1-positive patients with advanced non-small cell lung cancer in China."

About Repotrectinib

Repotrectinib is an investigational next-generation TKI designed to effectively target ROS1 and TRK A/B/C with potential to treat TKI-naïve or -pretreated patients. ROS1 rearrangement is estimated to be an oncogenic driver in approximately 2 to 3 percent of patients with advanced NSCLC in China, and NTRK is estimated to be an oncogenic driver in approximately 0.5 percent of patients with other advanced solid tumors in China.

Utilizing a 22 July 2019 data cut-off, data from the Phase 1 portion of TRIDENT-1 demonstrated the potential for repotrectinib to be best-in-class for the treatment of ROS1-positive advanced NSCLC in patients who were not previously treated with a TKI, with a 91 percent overall response rate by blinded independent central review, a median duration of response of 23.1 months, a median progression-free survival of 24.6 months, and a generally well-tolerated adverse-event profile.

HiberCell Announces Acquisition of Biothera Pharmaceuticals’ Imprime PGG Program

On July 7, 2020 HiberCell, a biotechnology company developing novel therapeutics for cancer relapse and metastasis, reported the acquisition of Biothera Pharmaceuticals’ (Biothera) Imprime PGG program (Press release, HiberCell, JUL 7, 2020, View Source [SID1234561714]). HiberCell will integrate Biothera’s Minnesota-based staff, operations and other assets into the company.

Imprime PGG is a novel innate immune activator that binds to the dectin-1 receptor and activates innate immunity, reprogramming the immunosuppressive tumor microenvironment to enhance antigen presentation, trigger T cell activation and ultimately enhance the immune response against tumors. Phase II clinical studies of Imprime PGG in combination with checkpoint inhibition demonstrated compelling mechanistic proof-of-concept data including the activation of innate and adaptive immunity resulting in improved overall survival, overall response and disease control rates in metastatic triple negative breast cancer (mTNBC).

"Imprime PGG has provided meaningful responses in Phase 2 clinical trials for metastatic cancer patients. HiberCell will build on these data and their potential to transform the lives of people living with metastatic breast cancer," said Alan C. Rigby, Ph.D., co-founder and chief executive officer of HiberCell. "This acquisition signifies HiberCell’s transition into a clinical stage company with a broad portfolio of assets targeting cancer relapse and metastasis."

HiberCell’s scientific approach focuses on three mechanistic pillars of cancer dormancy: adaptive stress biology, disseminated tumor cells and the tumor microenvironment. By exploring each, the company continues to assemble a pipeline of differentiated therapeutic opportunities for relapsed and metastatic cancer. Importantly, the Imprime PGG program adds to the HiberCell pipeline a later-stage innate immune activator supported by a robust translational oncology platform that has demonstrated a ‘reprogramming’ and activation of the tumor microenvironment.

In Phase II clinical studies, Imprime PGG paired with the checkpoint inhibitor Keytruda resulted in encouraging benefits across all clinical measures in patients with metastatic breast cancer, including TNBC. HiberCell will initiate additional clinical studies in TNBC and other indications to further demonstrate the safety and efficacy of various Imprime PGG combination therapies.

"We are very proud of the translational platform and science behind Imprime PGG," said Jeremy R. Graff, Ph.D., chief development officer of HiberCell. "We look forward to building a robust clinical pipeline in support of the meaningful data Imprime PGG has generated to date and are thrilled to continue this work at HiberCell."

Vor Biopharma Closes $110 Million Series B Financing

On July 7, 2020 Vor Biopharma, an oncology company pioneering engineered hematopoietic stem cells (eHSCs) for the treatment of cancer, reported it has raised $110 million in a Series B financing (Press release, Vor BioPharma, JUL 7, 2020, View Source [SID1234561713]). Proceeds will advance the company’s lead candidate VOR33 into clinical trials, deepen its portfolio, and accelerate the validation of additional targets for its scientific platform, which is designed to remove redundant proteins so that transplanted stem cells become invisible to targeted therapies while leaving diseased cells vulnerable. Vor’s treatment strategy has the potential to bring a revolutionary treatment paradigm for patients with acute myeloid leukemia and other hematologic malignancies.

"Vor has an elegant approach to engineering hematopoietic stem cells that we believe is amongst the most promising innovations in oncology," said Joshua Resnick, MD, Managing Director at RA Capital Management. "We are proud to support the efforts of their impressive team of experienced leaders and drug developers as they work aggressively to establish a new standard of care in stem cell transplants and forge ahead into first-in-human clinical studies."

RA Capital Management led the Series B financing, along with a diverse group of well-respected new investors including Fidelity Management & Research Company, LLC, Pagliuca Family Office, Alexandria Venture Investments, and other undisclosed investors, including additional institutional crossover investors. Existing investors 5AM Ventures, Johnson & Johnson Innovation — JJDC, Inc. (JJDC), Osage University Partners, and co-founder PureTech Health participated in the financing.

"The high caliber of investors participating in this financing underscores the tremendous potential of our eHSC platform," said Robert Ang, MBBS, MBA, Vor’s President and Chief Executive Officer. "We have ambitious goals for the coming year, and this financing is an important step as we prepare to treat cancer patients in our first clinical trials."

AbbVie to Host Second-Quarter 2020 Earnings Conference Call

On July 7, 2020 AbbVie (NYSE: ABBV) reported that it will announce its second-quarter 2020 financial results on Friday, July 31, 2020, before the market opens (Press release, AbbVie, JUL 7, 2020, View Source [SID1234561712]). AbbVie will host a live webcast of the earnings conference call at 8 a.m. Central time. It will be accessible through AbbVie’s Investor Relations website investors.abbvie.com. An archived edition of the session will be available later that day.