On August 17, 2023 Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company focused on novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases and cancer, reported that the Company has achieved an undisclosed milestone payment from Boston Pharmaceuticals (Press release, Pieris Pharmaceuticals, AUG 17, 2023, View Source [SID1234634480]). The milestone is based on dosing the first patient in a Boston Pharmaceutical-sponsored phase 1/2 study of BOS-342 (formerly PRS-342), a 4-1BB/GPC3 immuno-oncology antibody-Anticalin fusion (Mabcalin) bispecific protein, which was discovered by Pieris and licensed to Boston Pharmaceuticals and designed to provide a potent costimulatory bridge to exert tumor killing activity through the recruitment of T-cells.

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The open-label phase 1/2 study is designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of BOS-342. The Phase 1 dose escalation portion of the study is expected to enroll adults with hepatocellular carcinoma (HCC) that progressed on at least one prior treatment and establish a recommended Phase 2 dose. If pursued, the Phase 2 portion of the study will evaluate efficacy, as measured by overall response rate.

The study is funded and conducted by Boston Pharmaceuticals, who exclusively licensed worldwide rights to BOS-342 in April 2021. In addition to the milestone announced today, Pieris could potentially be entitled to receive up to approximately $350 million in development, regulatory and sales-based milestone payments, and tiered royalties on sales of BOS-342.

"We are delighted with Boston Pharmaceuticals’ commitment to BOS-342, now having initiated clinical development of yet another promising 4-1BB bispecific Mabcalin program originating from our platform and representing the fourth 4-1BB-targeted therapy that has entered clinical stage development," said Stephen S. Yoder, President and CEO of Pieris. "4-1BB is a highly promising target for cancer immunotherapy, and our multiple partnerships in this area validate the potential that 4-1BB-based bispecific therapies may play in advancing cancer therapeutics."

"Dosing of the first patient with BOS-342 represents an important milestone for the BOS-342 program and, more importantly, for patients with HCC, many of whom often do not achieve durable benefit from current available treatment regimens," said Sophie Kornowski, CEO of Boston Pharmaceuticals. "Preclinical data strongly support our belief that BOS-342 has the potential to address a significant unmet need as a treatment for patients with GPC3+ HCC."

On August 17, 2023 Nuvectis Pharma, Inc. (NASDAQ: NVCT) ("Nuvectis" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology, reported that NXP800 was granted Orphan Drug Designation by the United States Food and Drug Administration ("FDA") for the treatment of cholangiocarcinoma (Press release, Nuvectis Pharma, AUG 17, 2023, View Source [SID1234634478]).

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Ron Bentsur, Chairman and Chief Executive Officer of Nuvectis, commented, "We are pleased to have received this designation from the FDA for NXP800, which emphasizes the need for new, innovative therapies for the treatment of cholangiocarcinoma, a deadly malignancy with only limited treatment options available. NXP800 is an oral small molecule with a novel mechanism of action that has demonstrated robust activity in several preclinical cancer models, including ARID1a-mutated ovarian, endometrial and gastric carcinomas, as well as cholangiocarcinoma. The clinical activity of NXP800 is currently being evaluated in a Phase 1b clinical trial in patients with ARID1a-mutated ovarian carcinoma, with additional diseases planned for clinical investigations. This orphan drug designation is an important milestone in our journey toward our mission of developing NXP800 for the treatment of serious conditions of unmet medical need in oncology."

About Orphan Drug Designation

Orphan Drug Designation is granted by the FDA to drugs or biologics intended to treat a rare disease or condition, defined as one that affects fewer than 200,000 people in the United States. Orphan Drug Designation provides certain financial incentives to support clinical development, and the potential for up to seven years of marketing exclusivity for the product for the designated orphan indication in the United States if the product is approved for its designated indication.

About Cholangiocarcinoma

Cholangiocarcinoma is a cancer of the biliary tract originating in the epithelium of the biliary tree accounting for approximately 3% of all gastrointestinal malignancies, with an annual incidence of approximately 8,000 – 10,000 in the United States. Surgical resection is the only potentially curative treatment for cholangiocarcinoma, but the disease is often diagnosed as unresectable because of local extension and/or metastases. While several targeted therapies have been approved in recent years for subsets of patients with cholangiocarcinoma based on specific tumor genetics, the overall prognosis remains poor with 5-year survival rates of 20-50% after resection and almost 0% in unresectable tumors.

On August 17, 2023 NovaRock Biotherapeutics Ltd, announced today that the U.S. Food and Drug Administration (FDA) issued a "study may proceed" letter for its investigational new drug (IND) application for NBL-028, a CLDN6-CD137 BsAb T Cell Engager (Press release, NovaRock Biotherapeutics, AUG 17, 2023, View Source [SID1234634476]). The company plans a Phase I clinical study to evaluate the safety, tolerability, and pharmacokinetics of NBL-028 in patients with CLDN6 expressing advanced tumors, including but not limited to testicular cancer, ovarian cancer, non-small cell lung cancer (NSCLC) and endometrial cancer.

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About NBL-028

Claudin 6 is a member of the claudin family of tight junction (TJ) proteins and is expressed at high levels in multiple human malignancies but has little to no expression in normal tissues. CD137, or 4-1BB, a member of the superfamily of tumor necrosis factor receptors (TNFR), is an inducible co-stimulatory receptor that plays a key role in T cell proliferation, survival, cytolytic activity, and memory formation as well as modulating other immune cell functions. NBL-028 targets both human CLDN6 and human CD137. It is designed to selectively activate the CD137 co-stimulatory pathway in T cells and other immune cells upon binding to the tumor cell surface CLDN6 in TME, resulting in conditional redirected tumor cell killing. NBL-028 has demonstrated superior efficacy and safety in preclinical studies.

NBL-028 is the first program entering clinical phase from NovaRock’s proprietary T cell engager platform NovaTE. NovaTE is a next-generation T cell engager platform for treating cancer, especially solid tumors. NovaTE is designed and optimized to induce sustainable T effector cell activation, lift immune suppression in the TME, while minimizing the risk of systemic toxicity, including CRS, ICANS and hepatotoxicity. NBL-028 offers a potential advantage in the efficacy and safety for patients with CLDN6-expressing tumors.

NovaRock also filed an IND application to National Medical Products Administration (NMPA) in PRC in July 2023.

On August 17, 2023 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported that it will host a virtual KOL event on VAL-083, a potential first-in-class small molecule chemotherapeutic for glioblastoma, on Monday, August 21, 2023 at 11:00 AM ET (Press release, Kintara Therapeutics, AUG 17, 2023, View Source [SID1234634475]). To register for the event, click here.

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The event will feature Patrick Y. Wen, M.D. (Harvard Medical School) and John de Groot, M.D. (UCSF Health) who will discuss the current treatment landscape for patients suffering from glioblastoma (GBM), the most common and lethal form of brain cancer, along with Kintara’s potential treatment solution with VAL-083, a potential first-in-class small molecule chemotherapeutic.

Kintara is currently advancing VAL-083 in the GBM AGILE Study, which is an international registrational Phase II/III clinical study for GBM, with top-line data before the end of calendar 2023. VAL-083 has completed two open-label, biomarker-driven, Phase II studies in MGMT-unmethylated GBM. MGMT is a DNA-repair enzyme that is associated with resistance to temozolomide, the current standard-of-care chemotherapy used in the treatment of GBM.

A live question and answer session will follow the formal presentations. A replay will be available after the call at the link here.

ABOUT PATRICK Y WEN, M.D.

Patrick Y Wen, M.D. is a Professor of Neurology at Harvard Medical School, and Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute in Boston, MA. Dr. Wen serves as Co-PI of the National Cancer Institute supported Adult Brain Tumor Consortium, and member of the Steering Committee of the Response Assessment in Neuro-Oncology (RANO) Working Group. Dr. Wen graduated from the Medical College of St. Bartholomew’s Hospital, University of London. He completed his internal medicine training at the University of London ‘s postgraduate hospitals and his neurology residency in the Harvard-Longwood Neurology Training Program. His research is focused on novel treatments of brain tumors, especially targeted molecular agents. His other clinical interests include neurologic complications of cancer. Dr. Wen has authored or co-authored hundreds of peer-reviewed articles that have been published in journals such as Neurology, Neuro-Oncology, Current Opinion in Neurology, and Journal of Clinical Oncology. He serves as President of the Society for Neuro-Oncology and SNO Executive Editor of Neuro-Oncology.

ABOUT JOHN DE GROOT, M.D.

John de Groot, M.D. is a neuro-oncologist who specializes in diagnosing and managing the care of patients with primary brain and spine tumors (those at the site where disease began, as compared with tumors that result from the disease spreading). Dr. de Groot has brought new therapies from the laboratory into the clinic to treat patients with brain cancer. In particular, he has contributed to the development of glioblastoma treatments. He has a special interest in using blood analyses, imaging studies and other indirect biomarkers (measurable elements that may indicate disease) to evaluate the efficacy of novel therapies. In one study, he is looking at ways to overcome physiological limitations in drug delivery to brain tumors, such as through focused ultrasound. He regularly advises and collaborates with other researchers on promising therapies under development. Dr. de Groot earned his medical degree from the University of Texas Medical Branch at Galveston. He completed a residency in neurology at Johns Hopkins University and a fellowship in neuro-oncology at the University of Texas MD Anderson Cancer Center.

On August 17, 2023 Immatics N.V. (NASDAQ: IMTX; "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported a business update and announced financial results for the quarter ended June 30, 2023 (Press release, Immatics, AUG 17, 2023, View Source [SID1234634474]).

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"The interim clinical data update for IMA203 monotherapy demonstrated an encouraging initial objective response rate in a range of solid cancer indications including durable responses supporting fast-tracking IMA203 to patients, starting with high-need solid cancers such as checkpoint-refractory melanoma and uveal melanoma," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "Beyond our recent IMA203 updates, we are pleased to report that we closed the second quarter with a cash position funding operations into late 2025. With this revised runway, we anticipate reaching our most critical milestones including the initiation of registration-directed trials for IMA203, as well as delivering meaningful data to assess clinical proof of concept for both TCER programs IMA401 and IMA402."

Second Quarter 2023 and Subsequent Company Progress

Adoptive Cell Therapy Programs

ACTengine IMA203: ACTengine IMA203 TCR-T against PRAME is currently being evaluated in an ongoing Phase 1b dose expansion trial.

As per the latest data cut-off of April 4, 2023, ACTengine IMA203 TCR-T monotherapy Cohort A showed a 67% confirmed objective response rate (cORR) in an interim clinical update announced on May 2, 2023. The data covered 11 heavily pre-treated patients; the median duration of response was not reached at a median follow-up time of 8.5 months. Patients were infused with IMA203 TCR-T cells at dose level (DL) 4 or DL5 with a mean total infused dose of 3.67×109 TCR-T cells (range 1.30-8.84×109 TCR-T cells).
Cohort A IMA203 monotherapy TCR-T treatment continues to show manageable tolerability with no high-grade CRS and no ICANS; all 11 patients experienced expected cytopenia (Grade 1-4) associated with lymphodepletion. 10 patients (91%) had a low to moderate (Grade 1-2) cytokine release syndrome (CRS), of which 5 patients (45%) had Grade 1, and 5 patients (45%) had Grade 2 CRS.
Objective responses were observed independent of tumor type including checkpoint-refractory and BRAF inhibitor-refractory cutaneous melanoma, platinum-resistant ovarian cancer, uveal melanoma, head and neck cancer and synovial sarcoma. Longest duration of responses were observed in cutaneous and uveal melanoma with ongoing responses at 6, 9 and 10 months post infusion at data cut-off.
IMA203 in combination with nivolumab (Cohort B) has been de-prioritized in the last-line setting. Such a combination is being considered for the front-line setting.
IMA203CD8 (Cohort C) is a next-generation monotherapy where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor. IMA203CD8 is currently being explored in DL4a (up to 0.8×109 TCR-T cells/m2 BSA).
Next update on Immatics’ IMA203 Phase 1b cohorts, including the projected clinical development path for PRAME-targeted TCR-T monotherapy towards registration-directed trials is planned for 4Q 2023. Immatics’ IMA203 development strategy to realize the multi-cancer opportunity of targeting PRAME is based on two pillars aimed at:
maximizing speed to market in one to two last-line solid cancer types focusing on cutaneous melanoma, uveal melanoma and potentially other tumor types with high PRAME prevalence where clinical proof-of-concept has been demonstrated, and
broad development with expansion to other cancer types, such as ovarian cancer, uterine cancer, lung cancer, breast cancer, head and neck cancer and other tumor types having a broad patient reach.
TCR-T pipeline

Earlier this year, Bristol Myers Squibb exercised its first option and entered into a global license agreement with Immatics for the most advanced TCR-T product candidate. As part of the agreement, Immatics received an option payment of $15 million and is eligible for up to $490 million in milestone payments in addition to tiered royalties on net sales of the product.

TCR Bispecifics Programs

Immatics’ T cell engaging receptor (TCER) candidates are next-generation, half-life extended TCR Bispecific molecules designed to maximize efficacy while minimizing toxicities in patients through Immatics’ proprietary format using a low-affinity T cell recruiter and a high-affinity TCR domain.

TCER IMA401 (MAGEA4/8) – Phase 1 trial to evaluate safety, tolerability and initial anti-tumor activity of TCER IMA401 in patients with recurrent and/or refractory solid tumors is ongoing. IMA401 targets an HLA-A*02:01-presented peptide that occurs identically in two different proteins, MAGEA4 and MAGEA8. This target peptide has been selected based on natural expression in native solid tumors at particularly high target density (peptide copy number per tumor cell identified by Immatics’ proprietary quantitative mass spectrometry engine XPRESIDENT). MAGEA4 and MAGEA8 are expressed in multiple solid cancers including lung cancer, head and neck cancer, melanoma, ovarian cancer, sarcoma and others. IMA401 is being developed in collaboration with Bristol Myers Squibb.

TCER IMA402 (PRAME) – Immatics submitted a clinical trial application (CTA2) to the Paul-Ehrlich-Institute (PEI) in April 2023. Following CTA acceptance, Immatics initiated the Phase 1/2 trial investigating the company’s fully owned TCER candidate IMA402 in patients with recurrent and/or refractory solid tumors in August. Initial focus indications are cutaneous and uveal melanoma, ovarian cancer, lung cancer, uterine cancer and synovial sarcoma, among others. A first clinical data update is planned for 2024. IMA402 targets an HLA-A*02:01-presented peptide derived from the tumor antigen PRAME. This target peptide has been selected based on natural expression in native solid primary tumors and metastases at particularly high target density (peptide copy number per tumor cell identified by Immatics’ proprietary quantitative mass spectrometry engine XPRESIDENT).

Corporate Updates

On July 24, 2023, Bristol Myers Squibb purchased 2,419,818 ordinary shares in a private placement transaction at a subscription price per share of $14.463. Additionally, Bristol Myers Squibb will appoint a member to the Immatics Scientific Advisory Board.
Second Quarter 2023 Financial Results

Equity: The Company raised a total of $64 million in June through August through its ATM facility.

Cash Position: Cash and cash equivalents as well as other financial assets total €347.6 million ($377.7 million1) as of June 30, 2023, compared to €362.2 million ($393.6 million1) as of December 31, 2022. The decrease is mainly due to our ongoing research and development activities, partially offset by the option fee received by Bristol Myers Squibb and funds raised in the period. The Company projects an updated cash runway into late 2025.

Revenue: Total revenue, consisting of revenue from collaboration agreements, was €22.4 million ($24.3 million1) for the three months ended June 30, 2023, compared to €17.2 million ($18.7 million1) for the three months ended June 30, 2022. The increase is mainly related to the recognition of revenue for the opt-in agreement with Bristol Myers Squibb signed during the three months ended June 30, 2023.

Research and Development Expenses: R&D expenses were €27.3 million ($29.7 million1) for the three months ended June 30, 2023, compared to €25.2 million ($27.4 million1) for the three months ended June 30, 2022. The increase mainly resulted from higher costs associated with the advancement of the clinical and pre-IND pipeline of ACTengine and TCER candidates.

General and Administrative Expenses: G&A expenses were €9.4 million ($10.2 million1) for the three months ended June 30, 2023, compared to €8.7 million ($9.5 million1) for the three months ended June 30, 2022.

Net Profit and Loss: Net loss was €24.6 million ($26.7 million1) for the three months ended June 30, 2023, compared to a net loss of €14.0 million ($15.2 million1) for the three months ended June 30, 2022. The increased net loss mainly resulted from non-cash fair value adjustments of outstanding warrants.

Upcoming Investor Conferences

Jefferies Cell & Genetic Medicine Summit, New York, NY – September 26-27, 2023
Jefferies London Healthcare Conference, London, U.K. – November 14-16, 2023
To see the full list of events and presentations, visit View Source