On August 16, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported initiation of the first cohort of its Phase 1b/2 TRIDENT-2 combination study of lead investigational drug repotrectinib (Press release, Turning Point Therapeutics, AUG 16, 2021, View Source [SID1234586647]). The initial cohort will investigate repotrectinib in combination with MEK-inhibitor trametinib in KRAS G12D mutated advanced solid tumors.

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"We are pleased to initiate the TRIDENT-2 study and explore a potential new treatment option for patients with KRAS-driven solid tumors," said Mohammad Hirmand, executive vice president and chief medical officer. "With preclinical studies demonstrating repotrectinib’s ability to inhibit JAK2, SRC and FAK, our goal is to help improve the effectiveness of KRAS-targeting agents by suppressing known pathways of tumor resistance."

The Phase 1b portion of the study will examine the safety, tolerability, pharmacokinetics, and any early signals of efficacy of repotrectinib in combination with trametinib in patients with KRAS G12D mutated advanced solid tumors. After determination of a recommended Phase 2 combination dose, the study includes a Phase 2 dose expansion portion with the primary endpoint of objective response rate.

Results from preclinical studies presented at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting found that repotrectinib in combination with trametinib was more effective than single-agent trametinib in patient-derived KRAS mutant G12D lung cancer models. The repotrectinib-trametinib combination suppressed a broad range of downstream mutant KRAS G12D signaling, increased cell cycle arrest and induction of apoptosis, and was more active in multiple KRAS G12D dependent models compared to either single-agent treatment.

The frequently mutated Kirsten Rat Sarcoma (KRAS) viral oncogene is associated with a broad range of human cancers, including approximately 30% of non-small cell lung, 40% of colorectal and more than 90% of pancreatic cancers. KRAS G12D mutations are known to occur across multiple tumors types, including an estimated 30% of pancreatic, 15% of colorectal and 5% of both endometrial and non-small cell lung cancers.

Therapeutic targeting of KRAS has proven challenging, in part due to resistance and adaptive upregulation of alternative signaling pathways that promote tumor cell survival, as well as concurrent secretion of various cytokines and growth factors.

On August 16, 2021 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, reported that it has entered into a commercial manufacturing and supply agreement with Evergreen Theragnostics, a global radiopharmaceutical contract development and manufacturing organization (CDMO) based in Springfield, NJ (Press release, Cellectar Biosciences, AUG 16, 2021, View Source [SID1234586671]). The company also announced that the United States Adopted Names Council (USAN) has approved the use of "iopofosine I-131" as the generic name for CLR-131.

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The agreement with Evergreen provides long term commercial supply of iopofosine I-131 and supply of clinical study material for Cellectar’s pivotal study in Waldenstrom’s macroglobulinemia (WM) as well as ongoing Phase 1 and Phase 2 clinical studies. Evergreen will conduct process development and validation of additional large scale commercial quantities of iopofosine I-131 at its newly constructed, state-of-the-art manufacturing facility designed specifically for radiopharmaceutical manufacturing, including therapeutic and diagnostic radiopharmaceuticals.

"Establishing a collaboration with a strong partner capable of supplying clinical and commercial scale quantities of iopofosine I-131 is another important advancement in our iopofosine I-131 product development and commercialization plan," said James Caruso, president and CEO of Cellectar. "Evergreen has tremendous expertise as a leading radiopharmaceutical contract manufacturer, and their location in New Jersey provides strategic logistical advantages including favorable distribution for both the U.S. and ex-U.S. markets. Importantly, this collaboration expands upon our current supply capabilities with our existing CDMO, allows future development and supply of additional radiotherapeutic programs in development and continues to pave the way for Cellectar to meet the potential market demand for iopofosine I-131 upon approval."

James Cook, CEO of Evergreen Theragnostics stated that, "We welcome this new collaboration with Cellectar Biosciences. Iopofosine I-131 represents a unique and novel class of radiotherapeutics and Evergreen is excited to participate in its continued development and long-term supply to patients. We look forward to working with Cellectar on this and future programs."

Iopofosine I-131 is currently being investigated in a global, pivotal expansion cohort in WM patients who have received at least two prior lines of therapy, including Bruton tyrosine kinase inhibitor failed or suboptimal response. The WM cohort will enroll up to 50 patients to evaluate the efficacy and safety of iopofosine I-131 for marketing approval. The company is also evaluating iopofosine I-131 in highly refractory multiple myeloma patients in its Phase 2 CLOVER-1 study in hematologic malignancies.

On August 15, 2021 InxMed (Nanjing) Co., Ltd. ("InxMed" or "Company"), a clinical stage biotech company dedicated to developing innovative, individualized medicines with international impact, reported the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to IN10018 for the treatment of platinum-resistant ovarian cancer patients (Press release, InxMed, AUG 15, 2021, View Source [SID1234586586]). InxMed owns the global patent and development right of IN10018. The Fast Track designation for IN10018 underscores the urgent need for new treatment options for platinum-resistant ovarian cancer patients and the significant treatment potential of IN10018, it also further proves the InxMed’s world-class translational and clinical development capabilities.

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Ovarian cancer is the second most common cause of gynecologic cancer death in women in the world, with 23,820 new cases and 14,359 deaths in the United States and 55,342 new cases and 37,519 deaths in China in 2020 (GLOBOCAN 2020). Ovarian cancer is usually diagnosed at advanced stages. Surgery and platinum based chemotherapy are the main treatment regimens for ovarian malignant tumors. Although chemotherapy has a significant impact on patients primarily treated, these patients eventually develop platinum drug resistance, leading to a rapid progression. Once patients become platinum resistant, there is limited treatment option, and prognosis remain dismal with overall survival of one year. Both preclinical and clinical data from InxMed demonstrated IN10018’s promising efficacy when combining with standard chemotherapy to treat platinum-resistant ovarian cancer patients.

Dr. Zaiqi Wang, InxMed’s Chairman and CEO, said "This is an important milestone for InxMed. IN10018 is one of our critical assets to fulfill our "Best-in-Disease Combination" development strategy. We will leverage the advantage of Fast Track status and work closely with US FDA to speed up further clinical development. InxMed will fully accelerate global clinical development of IN10018 to better meet the patient’s needs."

About IN10018

IN10018 is a potent and selective ATP-competitive focal adhesion kinase (FAK) small molecule inhibitor under clinical development stage in United States, Australia, and China. InxMed owns the exclusive global rights for development and commercialization. Early clinical data of IN10018 has demonstrated a favorable safety profile and promising efficacy signals against a number of tumor types. Emerging science also showed that FAK inhibitors, like IN10018, potentially overcomes fibrotic barrier and immune tolerance, boosting multi-modalities including targeted therapy, chemotherapy, immune-therapy and radiation therapy.

On August 15, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported that the sintilimab Phase 3 ORIENT-16 study met its predefined primary endpoint of overall survival (OS) (Press release, Innovent Biologics, AUG 15, 2021, View Source [SID1234586587]). ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical trial evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine) compared to chemotherapy alone in the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

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In an interim analysis, sintilimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint of OS compared to placebo plus chemotherapy, in both the intention-to-treat (ITT) group and PD-L1 positive group. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy. These results will be presented at an upcoming medical meeting.

Based on the study’s Independent Data Monitoring Committee (IDMC) recommendation, Innovent plans to review these results and file a supplemental new drug application (sNDA) of sintilimab with the Drug Evaluation Center (CDE) of the National Medical Products Administration (NMPA) in China.

The principal investigator of the ORIENT-16 study, Prof. Jianming Xu from the Fifth Medical Center of People’s Liberation Army General Hospital, stated, "ORIENT-16 is the first Phase 3 clinical trial in China to demonstrate an anti-PD-1 antibody in combination with chemotherapy significantly prolonged overall survival in the first-line treatment of advanced gastric cancer. Gastric cancer is one of the most common malignant tumor types globally and nearly half of all cases are diagnosed in China. The prognosis of advanced gastric cancer is very poor. Currently, chemotherapy is the primary treatment option and targeted agents have offered limited benefit. The results of the ORIENT-16 study have the potential to bring a new and more effective treatment option to people with gastric cancer."

Dr. Zhou Hui, Senior Vice President of Clinical Development of Innovent, stated, "While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet in gastric cancer. The treatment options for advanced gastric cancer are very limited and the ORIENT-16 study aimed to help address this unmet medical need. These results are very encouraging and confirmed the clinical value of sintilimab plus chemotherapy in the first-line treatment of advanced gastric cancer. We are grateful for all the contributions made by every investigator and patient in this study, and we hope that sintilimab can become a treatment option for people with gastric cancer. Today, sintilimab is one of a few PD-1 inhibitors that has shown to be efficacious in the first-line treatment of five major types of cancer – nonsquamous non-small cell lung cancer, squamous non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer."

About the ORIENT-16 Study

ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (ClinicalTrials.gov, NCT03745170). The primary endpoint was overall survival, in all randomized and in PD-L1 positive patients.

About Gastric Cancer

Gastric cancer is one of the most common malignant tumor types worldwide. According to GLOBOCAN estimates, there were approximately one million new cases and 769,000 new deaths of gastric cancer in 2020, making it the fifth most common cancer and third leading cause of cancer death globally. About half of all gastric cancer cases occurred in East Asia, mainly in China. Platinum-based chemotherapy is still the primary option in the first-line treatment of advanced gastric cancer. Currently, the 5-year survival rate of advanced or metastatic gastric cancer ranges from 5 to 20 percent, and the median overall survival is approximately one year.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an 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. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has three clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
In combination with oxaliplatin and capecitabine for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

On August 13, 2021 HCW Biologics Inc. (the "Company") (NASDAQ: HCWB), an innovative, biopharmaceutical company focused on discovering and developing novel immunotherapies to lengthen health span by disrupting the link between chronic, low-grade inflammation and age-related diseases, reported financial results and recent business highlights for its second quarter ended June 30, 2021 (Press release, HCW Biologics, AUG 13, 2021, View Source [SID1234586547]).

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"HCW Biologics delivered on a milestone as we achieved our goal of closing our initial public offering on July 22 to raise capital to advance the clinical development of our lead molecules," stated Hing C. Wong, Ph.D., founder and CEO of HCW Biologics Inc. "We started HCW Biologics three years ago with an idea to develop immunotherapeutic treatments for age-related diseases. Since that time, we applied our expertise in advanced protein engineering to internally develop our TOBITM (Tissue factOr-Based fusIon) discovery platform and successfully developed immunotherapeutic molecules based on TOBITM technology that can be administered by subcutaneous injection as well as used in adoptive cell therapy approaches. After extensive studies to assess the molecules we created, we selected two lead molecules, HCW9218 and HCW9302 for clinical development."

"HCW Biologics’ clinical development strategy is to prove the safety and efficacy of both lead molecules individually in future clinical trials, and eventually combine them as an immunotherapeutic for some of the most difficult to treat age-related diseases. Our gateway indication for our lead molecule, HCW9218, is cancer. Several scientific studies have revealed that increased normal tissue cellular senescence can promote tumor progression, creating a link between aging and cancer. In preclinical studies, HCW9218 has shown it can reduce chemotherapy-induced tumor and normal tissue senescence and decrease senescence associated secretory phenotype (i.e., proinflammatory) factors that senescent cells secrete, in particular TGF-ß. We are wrapping up IND-enabling activities and expect to submit an Investigational New Drug (IND) application for a Phase 1b/2 clinical trial to assess HCW9218 in the treatment of pancreatic cancer by the end of 2021."

Business Highlights:

Initial Public Offering: On July 22, 2021, the Company closed on its IPO with the sale of 7,000,000 shares of common stock at a public offering price of $8.00 per share, resulting in net proceeds of approximately $49.0 million, after deducting underwriting discounts and commissions and estimated offering-associated expenses.

As part of the preparations of becoming a public company, HCW Biologics shareholders elected two new independent board members in May 2021. Mr. Scott Garrett serves as the Chairman of the Board and Chairman of the Compensation Committee. His experience as a Chief Executive Officer and in other senior leadership positions with biomedical and diagnostics companies enables him to bring to the Board of Directors an operational perspective as well as valuable insights and experience. Mr. Rick Greene serves as the Chairman of the Audit Committee. His experience as a Chief Financial Officer and in other financial management and reporting, operations and business development positions in the healthcare industry enables him to bring financial expertise to the Board of Directors. The Company is committed to expanding the size of its Board of Directors to bring additional diversity and operational expertise.

As of June 30, 2021, the Company completed good laboratory practice (GLP) toxicology studies on nonhuman primates and mice to understand the onset, degree of severity, and time length up to which a particular dose of a drug demonstrates any toxic effects. The Company will continue to complete IND-enabling activities for HCW9218 and prepare for the IND filing in the second half of 2021.

The Company launched the execution of its strategy to use pivotal publications to establish its leadership in oncology and age-related diseases in scientific and clinical communities. The Company currently has two articles published online:

An article published online by Cancer Immunology Research describing the TOBITM discovery platform: Becker-Hapak MK, et al. A Fusion Protein Complex Combines IL-12, IL-15, and IL-18 Signaling to Induce Memory-like NK Cells for Cancer Immunotherapy. July 9, 2021.
An article published online by Molecular Therapy on the characterization of the Company’s lead molecules, HCW9218: Liu B et al. Bifunctional TGF-β Trap/IL-15 Protein Complex Elicits Potent NK Cell and CD8+ T Cell Immunity Against Solid Tumors. June 3, 2021.
Second Quarter Financial Results:

Cash and cash equivalents: On June 30, 2021, the Company’s cash balance was $5.1 million. Together with net proceeds of $49.0 million from the IPO, the Company estimates that it has sufficient cash to fund operations and capital expenditures for at least the next 24 months. This does not include potential sources of non-dilutive financing, which may be obtained as a result of entering out-licenses, such as upfront cash payment and shares of Wugen common stock that were received as a result of entering a license agreement with Wugen for limited rights to two of the Company’s molecules.
Research and development expenses: Research and development expenses were $1.7 million in the second quarter of 2021, as compared to $2.1 million for the second quarter of 2020. Higher costs in the second quarter of 2020 were a result of the ramp up costs required for initiation of cGMP manufacturing for five of the Company’s internally developed molecules.
General and administrative expenses: General and administrative expenses were $1.1 million in the second quarter of 2021, as compared to $0.7 million for the second quarter of 2020. The difference reflects additional general and administrative costs arising primarily from additional patent filings to broaden the protection of the Company’s intellectual property and performance-based bonuses.
Net loss: Net loss was $2.8 million in the second quarter of 2021, as compared to $2.8 million for the second quarter of 2020.