On January 19, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported the presentation of the study design for its phase III trial, COMPOSE (NCT04919226), at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI), held from January 20 – 22, 2022 (Press release, , 19 19, 2022, View Source [SID1234605661]). COMPOSE will evaluate the company’s lead radiopharmaceutical candidate, ITM-11 (n.c.a. 177Lu-edotreotide), compared to best standard of care in patients with well‐differentiated high grade 2 and grade 3 somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (G2+G3 SSTR+ GEP-NETs). ITM-11 consists of the high-quality radioisotope, no-carrier-added lutetium-177 (n.c.a. 177Lu) chelated to the somatostatin analogue edotreotide. The aim of the study, in which patients are currently being randomized, is to evaluate the efficacy and safety of the Targeted Radionuclide Therapy in this high-need indication. COMPOSE is ITM’s second phase III trial with ITM-11 following and building upon COMPETE (NCT03049189), in patients with grade 1 and grade 2 GEP-NETs. Sponsor of the COMPOSE study is ITM’s subsidiary ITM Solucin GmbH.

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"We look forward to presenting the study design of COMPOSE to the medical and scientific community at ASCO (Free ASCO Whitepaper)-GI given the significant potential of ITM-11 as an innovative treatment modality"

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"We look forward to presenting the study design of COMPOSE to the medical and scientific community at ASCO (Free ASCO Whitepaper)-GI given the significant potential of ITM-11 as an innovative treatment modality," commented Philip E. Harris, MD PhD, Chief Medical Officer at ITM. "The favorable safety profile and efficacy signals observed to-date with our lead candidate give us reason to believe that ITM-11 can provide an important clinical benefit to patients diagnosed with this high-need indication and an advanced stage of this cancer."

COMPOSE (NCT04919226) is an international, prospective, randomized, controlled, open-label, multi-center phase III clinical trial to evaluate the efficacy, safety, and patient-reported outcomes of first or second-line treatment with ITM-11 compared to best standard of care in patients with well-differentiated high grade 2 and grade 3 (Ki-67 index 15-55), SSTR+ GEP-NETs. The study aims to randomize 202 patients 1:1 to ITM-11 or to best standard of care — either chemotherapy (CAPTEM or FOLFOX) or everolimus — according to the investigator’s choice. The primary endpoint of the study is progression-free survival (PFS), which will be assessed every 12 weeks from randomization onwards. Secondary outcome measures include overall survival (OS) up to two years after disease progression.

"With poor prognoses and limited treatment options for GEP-NETs, COMPOSE is an important step toward addressing a patient population with a high unmet medical need," commented Thorvardur Ragnar Halfdanarson, Principal Investigator of COMPOSE at the Mayo Clinic, Rochester, MN, USA. "Targeted Radionuclide Therapy continues to demonstrate promise for the treatment of hard-to-treat tumors. As such, I look forward to investigating its potential for patients with advanced GEP-NETs as we move ITM-11 through this Phase III trial."

Presentation information

Title: Pivotal phase III COMPOSE trial will compare 177Lu-edotreotide with best standard of care for well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumor

Abstract No: TPS514

Poster No: P5

Session: Trials in Progress Poster Session B: Pancreas, Small Bowel, and Hepatobiliary Tract

Presenter: Thorvardur Ragnar Halfdanarson, Mayo Clinic, Rochester, MN, USA

– End –

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule (e.g., peptide, antibody, small molecule) that can precisely recognize tumor cells and bind to tumor-specific characteristics, like receptors on the tumor cell surface. As a result, the radioisotope accumulates at the tumor site and decays, releasing a small amount of ionizing radiation, thereby destroying tumor tissue. The highly precise localization enables targeted treatment with minimal impact to healthy surrounding tissue.

About ITM-11 (n.c.a. 177Lu-edotreotide)

ITM-11, ITM’s therapeutic radiopharmaceutical candidate being investigated in the phase III clinical studies COMPETE and COMPOSE, consists of two components: the medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu) and the targeting molecule edotreotide, a synthetic form of the peptide hormone somatostatin that targets neuroendocrine tumor-specific receptors. Edotreotide binds to these receptors and places the medical radioisotope n.c.a. lutetium-177 directly onto the diseased neuroendocrine cells so that it accumulates at the tumor site. N.c.a. lutetium-177 is internalized into the tumor cells and decays, releasing medical radiation (ionizing β-radiation) with a maximum radius of 1.7 mm and destroying tumor tissue. The highly precise localization can result in the healthy tissue surrounding the targeted tumor being minimally affected.

On January 19, 2022 Marker Therapeutics, Inc. (NASDAQ:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that the United States Food and Drug Administration (FDA) Office of Orphan Products Development has granted Orphan Drug designation to MT-601, a multi-tumor-associated antigen (MultiTAA)-specific T cell product optimized for the treatment of patients with pancreatic cancer.

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"The FDA’s orphan drug designation underscores MT-601’s potential as a treatment for pancreatic cancer, a cancer typically diagnosed at an incurable advanced stage with a total overall 5-year survival rate of 10%," said Peter L. Hoang, President & CEO of Marker Therapeutics. "Our novel therapy has shown encouraging results in an ongoing Phase 1 trial sponsored by Marker’s partners at the Baylor College of Medicine. In results reported at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting, our therapy has demonstrated the potential to safely produce durable responses in combination with chemotherapy as a first-line treatment option for patients with advanced or metastatic pancreatic adenocarcinoma. The results also revealed that epitope spreading was consistent in responders to Multi-TAA-specific T cells. Following MT-401 for the treatment of post-transplant acute myeloid leukemia (AML), MT-601 is Marker’s second novel MultiTAA-specific T cell product to receive orphan drug designation and the first in a solid tumor indication, underscoring the potential of Marker’s multi-antigen targeting T cell therapy approach in both solid tumors and blood cancers."

Marker developed MT-601, a new product targeting six tumor-associated antigens (PRAME, NY-ESO-1, Survivin, MAGE-A4, SSX2, WT1) highly expressed in pancreatic cancer. The Company intends to initiate a Phase 1 multicenter study of MT-601 administered in combination with front-line chemotherapy to patients with locally advanced unresectable or metastatic pancreatic cancer. Marker designed the study to include an initial antigen escalation period followed by a dose escalation period and will enroll 20 – 25 patients for the study.

The Company plans to file an Investigational New Drug Application (IND) for MT-601 for the treatment of pancreatic cancer in 2022.

Orphan designation is granted by the FDA Office of Orphan Products Development to advance the evaluation and development of safe and effective therapies for the treatment of rare diseases or conditions affecting fewer than 200,000 people in the U.S. Under the Orphan Drug Act, the FDA may provide grant funding toward clinical trial costs, tax credits, FDA user-fee benefits, and seven years of market exclusivity in the United States following marketing approval by the FDA. The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. For more information about orphan designation, please visit the FDA website at www.fda.gov.

On January 19, 2022 Panavance Therapeutics Inc. ("Panavance") reported an abstract and poster at ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, January 20-22, 2022, in San Francisco, "A Phase 1/2 study to evaluate the safety, tolerability, and preliminary efficacy of GP-2250 in combination with gemcitabine for advanced or metastatic pancreatic adenocarcinoma," (authors: Dr. Anup Kasi and Dr. José Iglesias, Poster TPS620) (Press release, Panavance Therapeutics, JAN 19, 2022, View Source [SID1234605663]). The open-label trial for patients with advanced/metastatic pancreatic cancer who were previously treated with FOLFIRINOX is evaluating the safety and tolerability of escalating doses of GP-2250 together with gemcitabine.

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GP-2250 is a broadly active, tumor cell selective, small molecular weight, metabolic enzyme inhibitor with a first-in-class mechanism of action that limits aerobic glycolysis and Krebs cycle by inhibiting GAPDH, alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and the tumor promotor NFkB. In preclinical research, it suppresses cancer cells largely by disrupting their energy metabolism—bringing about cancer cell death.

The ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium abstract and poster describe a dose-escalation trial of GP-2250 (NCT03854110) in combination with gemcitabine in the 2nd-line treatment of metastatic pancreatic cancer patients who have progressed on or after FOLFIRINOX in the 1st-line treatment of the disease. The primary endpoints in the trial are the maximum tolerated dose ("MTD") and recommended Phase 3 dose.

"To date, we believe our GP-2250 has demonstrated strong effectiveness and safety in extensive preclinical studies, and its early clinical results have been encouraging for its initial indication for pancreatic cancer," said Greg Bosch, Chairman & Chief Executive Officer of Panavance. "We’re pleased with the progress of our ongoing Phase 1 trial which is currently at the 6th dose level with more than 20 patients enrolled thus far."

While Panavance’s initial area of focus is on pancreatic cancer, the company is conducting additional preclinical research in several other tumor types and expects to progress clinical development of GP-2250 for the treatment of other cancers.

Learn more about Panavance and GP-2250 at www.panavance.com.

References and links to websites have been provided for convenience, and the information contained on any such website is not a part of, or incorporated by reference into, this press release. Panavance is not responsible for the contents of third-party websites.

On January 19, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated therapeutics, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for CX-904, an EGFRxCD3 T-cell-engaging bispecific antibody being co-developed by CytomX and Amgen (Press release, CytomX Therapeutics, JAN 19, 2022, View Source [SID1234605575]).

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"The impressive innovation of CX-904’s design and its advancement into the clinical setting underscores our commitment to destroying cancer differently. The CX-904 IND also marks the sixth therapeutic candidate and the third treatment modality overall to enter the clinic from our versatile and tunable Probody platform, reinforcing our leadership in the field of conditional activation of biologic therapeutics," said Sean McCarthy, D.Phil., president, chief executive officer and chairman of CytomX Therapeutics. "Our masked Probody T-cell engagers are designed to harness the power of this highly potent modality. We are eager to initiate the Phase 1 dose-escalation study for CX-904 as the leading edge of our broad efforts to bring conditionally activated bispecifics to patients with advanced solid tumors."

T-cell-engaging bispecific antibodies have tremendous potential for the treatment of solid tumors by directing T cells against tumor antigens, including the epidermal growth factor receptor (EGFR). However, the extraordinarily high potency of these agents can narrow their therapeutic window significantly when their target is present on normal tissues. CX-904 is a conditionally activated T-cell bispecific antibody designed to bind to both EGFR on cancer cells and to the CD3 receptor on T cells selectively in the tumor microenvironment. In preclinical studies, CytomX’s conditionally activated Probody EGFRxCD3 bispecific therapeutics demonstrated potent anti-tumor activity and strong improvement in safety versus EGFRxCD3 bispecifics without Probody masking.1

On January 20, 2022 ImmPACT Bio USA, Inc. ("ImmPACT Bio"), a clinical-stage company developing transformative logic-gate based chimeric antigen receptor (CAR) T-cell therapies for treating cancer, reported that it has closed $111 million in Series B financing, led by venBio Partners along with co-leads Foresite Capital and Decheng Capital (Press release, ImmPACT-Bio, JAN 19, 2022, View Source [SID1234605608]). Surveyor Capital (a Citadel company) also joined this financing round. Additional investors include the company’s existing investors OrbiMed, Novartis Venture Fund, RM Global Partners (RMGP), and Bukwang Pharmaceutical. The company also announced the appointment of Sheila Gujrathi, M.D., as chair of its board of directors, and Sumant Ramachandra, M.D., Ph.D., M.B.A., as president and chief executive officer (CEO), who will also join ImmPACT Bio’s board.

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In addition, ImmPACT Bio provided an update to the Phase 1 clinical study evaluating its CD19-CD20 bi-specific CAR T in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (R/R B-cell NHL) at University of California, Los Angeles (UCLA). In a total of eight patients treated to date with 12 months median followup, seven patients achieved and remain in complete remission (CR). A favorable tolerability profile was noted with no treatment-related neurotoxicity and no cytokine release syndrome above grade 1. Data will be presented in a future scientific forum.

The company’s logic-gate based CAR T platforms address key biological challenges in treating cancer. ImmPACT Bio’s technologies are specifically designed to address antigen escape, ‘on-target – off-tumor’ toxicities, and the immunosuppressive tumor microenvironment. The company’s technologies are based on the work of pioneering scientists Yvonne Chen, Ph.D., and Antoni Ribas, M.D., Ph.D., both from UCLA, and Gideon Gross, Ph.D., from the MIGAL-Galilee Research Institute. Proceeds from the financing will be used to further the company’s development of logic-gate-based CAR T-cell platforms.

"ImmPACT Bio is thrilled to receive such strong support from this outstanding group of investors," said newly appointed ImmPACT Bio CEO Dr. Ramachandra. "We are encouraged by these initial results of our Phase 1 clinical study and look forward to advancing our pipeline of transformative next-generation CAR T-cell therapies that harness the immune system and address key challenges for current cell therapies in cancer."

"We believe ImmPACT Bio’s technology platforms will help to expand the curative potential of cell therapies in certain cancers and to address challenges that have limited the efficacy of cell therapies in hard-to-treat tumor types," said Richard Gaster, M.D., Ph.D., managing partner at venBio Partners. "We are excited to work with the scientists and clinicians at ImmPACT Bio to translate their engineering innovations into novel cell therapy products for multiple malignancies."

"We’re honored to work with ImmPACT Bio as they develop novel strategies to address unmet oncology needs," said Jim Tananbaum, founder and CEO of Foresite Capital. "With Drs. Gujrathi and Ramachandra at the helm, this is an incredibly exciting time for ImmPACT Bio and the patients who are waiting for next-generation cancer therapies."

"ImmPACT Bio’s logic-gate-based CAR T platform holds tremendous potential to usher in a step-change in the treatment of solid tumors and blood cancers. We are pleased to join this distinguished group of healthcare investors supporting this world-class team to advance what we believe could become a new paradigm in cancer treatment," said Min Cui, Ph.D., founder and managing director of Decheng Capital.

As part of the financing, Yvonne Yamanaka, Ph.D., of venBio Partners, Cindy Xiong, Ph.D., of Foresite Capital, and Min Cui, Ph.D., of Decheng Capital will join the company’s board.

Sheila Gujrathi Named New Chair of Board of Directors

ImmPACT Bio also announced the appointment of Dr. Gujrathi as board chair. Erez Chimovits, partner at OrbiMed and ImmPACT Bio’s chairman, will remain on the company’s board.

"It is my pleasure to welcome Sheila to the board of ImmPACT Bio," said Mr. Chimovits. "This is a transformational period in ImmPACT Bio’s evolution, and Sheila is an exceptional fit for the company’s next stage of growth, given her deep experience leading biotech companies."

"ImmPACT Bio possesses an innovative and proprietary CAR T-cell platform, compelling clinical and early-stage assets, and a dynamic leadership team. Today’s announcement of the company’s Series B financing bolsters the potential to transform the oncology therapeutic landscape," said Dr. Gujrathi. "I’m thrilled to join as board chair and help ImmPACT Bio achieve its vision of developing transformative oncology medicines for cancer patients who have exhausted their treatment options."

Dr. Gujrathi is currently a venture advisor at OrbiMed and serves as executive chair of Ventyx Biosciences, chair of ADARx Pharmaceuticals, and director of Janux Therapeutics. She previously served as chair of Turning Point Therapeutics and is the co-founder and former CEO of Gossamer Bio. Prior to Gossamer, Dr. Gujrathi served as chief medical officer of Receptos, which was acquired by Celgene. Previously, she held development leadership positions at Bristol-Myers Squibb and Genentech where she led development and numerous global regulatory filings and approvals for immunology and oncology programs. Earlier in her career, she was a management consultant in McKinsey & Company’s healthcare practice. Dr. Gujrathi received both her M.D. in the accelerated Honors Program in Medical Education and her B.S. in biomedical engineering with highest distinction from Northwestern University. She completed her internal medicine internship and residency at Brigham and Women’s Hospital and Harvard Medical School and additional fellowship training in allergy/immunology at University of California, San Francisco (UCSF) and Stanford University Medical Center.

Industry Veteran Sumant Ramachandra Named President and CEO

Dr. Ramachandra brings more than 30 years’ experience in healthcare, including more than two decades in the pharmaceutical and medical device industry across multiple roles. CEO Rick Kendall, Ph.D., will continue as chief scientific officer (CSO) of ImmPACT Bio.

"I am confident ImmPACT has selected in Sumant the right leader to build on our success to date and to drive value for the company as he has done for several companies in the healthcare industry," said Dr. Gujrathi. "I want to thank Rick for his leadership in bringing ImmPACT Bio forward to a clinical-stage company and I look forward to working closely with this ‘dream team’ and contributing to our continued growth."

"I am excited to join ImmPACT Bio at such a crucial time in our development. I am impressed with the strong scientific foundation that the co-founders, management team, and board have built across its programs and platforms that aim to bring curative therapies to patients living with cancer," said Dr. Ramachandra.

Prior to joining ImmPACT Bio, Dr. Ramachandra was chief science, technology, and medical officer at Baxter International, which he joined in June 2017. In addition to these responsibilities, he was appointed president of Baxter Global Pharmaceuticals in mid-2019 and was appointed as chair of Baxter’s Global Inclusion Council focused on inclusion and diversity. Previously, he was at Pfizer, most recently as senior vice president, head of research and development, Pfizer Essential Health. He served as CSO at Hospira from 2008 to 2015 prior to Pfizer’s acquisition of Hospira in 2015. Earlier in his career, Dr. Ramachandra worked with Pfizer and Merck & Co. in various senior-level oncology global product development, medical affairs, and business development and licensing roles, and as a clinical pharmacologist. Before entering the industry in 2000, he was an intern and resident physician at Massachusetts General Hospital and Harvard Medical School.

Dr. Ramachandra earned a Ph.D. in experimental pathology in the study of chronic lymphocytic leukemia (CLL), an M.D., and a B.A. in biochemistry at Rutgers University. In addition, he holds an M.B.A. from the Wharton School of the University of Pennsylvania.

Leading the Next Generation of CAR T

For hematological malignancies, the company’s lead program is a CD19-CD20 bispecific ‘OR-gate’ CAR T designed to address antigen escape, which is a key challenge for current approved CD19 therapies. Early results indicate the potentially best-in-class bispecific CAR T-cell candidate is safe and effective in patients with R/R B-cell NHL.

Treating solid tumors is even more challenging, partially due to off-target safety considerations and the immunosuppressive tumor microenvironment. ImmPACT Bio is developing novel strategies for addressing this unmet need, designing next-generation CAR T to assure tumor specificity and efficacy in the hostile tumor environment, while protecting the normal tissue.

ImmPACT Bio’s second platform features engineered T cells with an activator/inhibitor ‘NOT-gate’ CAR combination that uniquely differentiates between tumor and normal cells. The activator CAR kills the tumor cells while the inhibitory CAR protects normal cells. The activator/inhibitor platform technology has the potential to deliver multiple products across solid tumors by pairing different activator/inhibitor combinations, providing diverse opportunities in an emerging and promising area of cancer therapy.

The company’s third platform, a TGF-β CAR that can be modularly equipped with tumor-targeting binding domains to generate bispecific ‘OR-gate’ CARs, rewires the T-cell response to TGF-β to convert this potent immunosuppressive cytokine into a T-cell stimulant. Single-chain bispecific CARs that simultaneously convert TGF-β signaling while directly targeting surface-bound tumor antigens enable T cells to robustly eliminate tumor cells in otherwise highly immunosuppressive microenvironments.