On July 20, 2023 HUTCHMED (China) Limited reported that the Center for Drug Evaluation of China’s National Medical Products Administration ("NMPA") has granted Breakthrough Therapy Designation ("BTD") to the combination of fruquintinib and sintilimab (a PD-1 antibody) for the treatment of patients with advanced endometrial cancer ("EMC") with pMMR1 tumors that have failed at least one line of platinum-based therapy (Filing, 6-K, Hutchison China MediTech, JUL 20, 2023, View Source [SID1234633327]). A study for potential registration of this combination in patients with previously treated advanced EMC in China has recently completed enrollment.

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It is a multi-center, open-label clinical study to evaluate the efficacy and safety of fruquintinib in combination with sintilimab. Entry criteria include those EMC patients who experienced disease recurrence, disease progression or grade 3 or higher serious adverse events with treatment on platinum-based chemotherapy. The primary endpoint is independent review committee (IRC) assessed objective response rate ("ORR"), with secondary endpoints including disease control rate ("DCR"), progression free survival ("PFS"), overall survival ("OS"), as well as pharmacokinetic (PK) assessments. A total of 142 previously treated, advanced EMC patients were enrolled. Additional details may be found at clinicaltrials.gov, using identifier NCT03903705.

Favorable results from this trial could lead to submission to the NMPA in the first half of 2024 for regulatory approval in this treatment setting.

About Breakthrough Therapy Designation in China

NMPA grants BTD to new drugs that treat life-threatening diseases or serious conditions for which there are no effective treatment options, and where clinical evidence demonstrates significant advantages over existing therapies. Drug candidates with BTD may be considered for conditional approval and priority review when submitting a New Drug Application ("NDA"). This indicates that the development and review of the therapy for this disease indication may be expedited, to address patients’ unmet needs more quickly.

About EMC

EMC is a type of cancer that begins in the uterus. Globally, an estimated 417,000 people were diagnosed with EMC and it caused approximately 97,000 deaths in 2020.2 Іn China, an estimated 82,000 people were diagnosed with EMC and it caused approximately 17,000 deaths in 2020.3 Although early-stage EMC can be surgically resected, recurrent and/or metastatic EMC remains an area of high unmet need with poor outcomes and limited treatment options.4,5,6

About Fruquintinib

Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptor ("VEGFR") -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity with the intention of minimizing off-target toxicities, improving tolerability and providing more consistent target coverage. Fruquintinib has been generally well tolerated in patients to date and is being investigated in combinations with other anti-cancer therapies.

Fruquintinib was approved for marketing by the NMPA in September 2018 and commercially launched in China in November 2018 under the brand name ELUNATE for the treatment of patients with metastatic colorectal cancer ("CRC") who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-epidermal growth factor receptor (EGFR) therapy (RAS wild type). It has been included in the National Reimbursement Drug List ("NRDL") since January 2020.

The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated.

Filing of a rolling submission of NDA to the U.S. Food and Drug Administration ("FDA") was accepted and granted priority review in May 2023 with a Prescription Drug User Fee Act (PDUFA) date of November 30, 2023. Submission to the European Medicines Agency (EMA) was validated in June 2023, and submission to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) is expected to be completed in 2023. The submissions to the FDA and the EMA include results from the Phase III FRESCO-2 trial along with data from the Phase III FRESCO trial conducted in China. FRESCO-2 is a global Phase III multi-regional clinical trial (MRCT) conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus best supportive care ("BSC") vs. placebo plus BSC in patients with previously treated metastatic CRC. The FRESCO-2 trial met its primary and key secondary endpoints, showing a significant and clinically meaningful improvement in OS and PFS, respectively. Fruquintinib has been generally well tolerated in patients to date (NCT04322539).7

An NDA to the NMPA was accepted in April 2023 for fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric or gastroesophageal junction adenocarcinoma. The NDA includes results from the Phase III FRUTIGA trial, a study in China to evaluate fruquintinib combined with paclitaxel compared with paclitaxel monotherapy in this patient population. Its dual-primary endpoints were PFS and OS. The trial met the PFS endpoint at a statistically and clinically meaningful level, and while there was an improvement in median OS, the OS endpoint was not statistically significant. Statistically significant improvements were also shown in secondary endpoints including ORR, DCR and duration of response (DoR). The safety profile was consistent with previously reported studies (NCT03223376).

HUTCHMED is also developing fruquintinib in China for the treatment of multiple other solid tumor cancers in combination with anti-PD-1 monoclonal antibodies. Fruquintinib is licensed to Takeda Pharmaceutical Company Limited outside of China. HUTCHMED markets fruquintinib in China in partnership with Eli Lilly and Company.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent Biologics, Inc. and Eli Lilly and Company. Sintilimab is a type of 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.8 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 seven indications and included in the NRDL for six indications.

On July 19, 2023 Panbela Therapeutics, Inc., a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported it has divested certain assets in its eflornithine pediatric neuroblastoma program to US WorldMeds1 (USWM), a Kentucky-based specialty pharmaceutical company (Press release, Panbela Therapeutics, JUL 19, 2023, View Source [SID1234633326]).

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Neuroblastoma, a rare cancer originating from immature nerve cells, contributes to nearly 15% of pediatric cancer deaths.[1] Panbela Therapeutics’ subsidiary, Cancer Prevention Pharmaceuticals, has extensively collaborated with leading neuroblastoma research groups such as the Neuroblastoma Medulloblastoma Translational Research Consortium (NMTRC) (now Beat Childhood Cancer), New Advances in Neuroblastoma Therapy (NANT), the Children’s Oncology Group (COG), and the National Cancer Institute (NCI) in the clinical development of eflornithine as a treatment for neuroblastoma. These collaborative efforts, spanning multiple years, have resulted in the Company receiving orphan drug designations for the use of eflornithine in the treatment of neuroblastoma in both the United States and Europe.

Under the terms of the agreement, Panbela is entitled to receive up to approximately $9.5 million non-dilutive funding in exchange for the sale of certain assets within its pediatric neuroblastoma program for eflornithine. Panbela will receive payments upon USWM’s successful completion of milestones related to eflornithine’s clinical development, regulatory approval, and commercial sales.

"Divesting eflornithine assets for pediatric neuroblastoma is another milestone in executing our business plan to generate long-term value for our shareholders. US WorldMeds’ existing focus in neuroblastoma makes them an ideal company to further its clinical development in that indication," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "This agreement further expands our portfolio of partner-funded programs and has the potential to generate considerable development milestone payments. We welcome US WorldMeds to our portfolio of partners who continue the development of our product candidates."

"We are excited that the agreement will help address this high unmet need through the further development of eflornithine for the treatment of patients with neuroblastoma," said Elizabeth Bruckheimer, Ph.D., Vice President & Chief Scientific Officer of Panbela. "After investigating the role of polyamines and the therapeutic potential of eflornithine in neuroblastoma for many years, it is comforting to be passing the baton to the capable hands at USWM. We look forward to helping USWM with the ongoing FDA review of their New Drug Application for eflornithine and future research efforts for patients with neuroblastoma."

"This transaction strengthens and expands our neuroblastoma program data currently under FDA review and builds upon our established partnerships to fully unleash the potential of DFMO as a breakthrough treatment for neuroblastoma," commented Paul Breckinridge Jones, Chief Executive Officer of US WorldMeds. "Our agreement with Panbela supports our overarching objective of redefining the standard of care and significantly improving outcomes for children with this devastating disease, who are in urgent need of new therapies."

About our Pipeline
The pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of catalysts with programs ranging from pre-clinical to registration studies.

SBP-101 Ivospemin
Ivospemin is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. It has shown signals of tumor growth inhibition in clinical studies of metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, both exceeding what is typical for the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, ivospemin has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the previous Panbela-sponsored clinical trials provide support for continued evaluation of ivospemin in the ASPIRE trial. For more information, please visit View Source .

Flynpovi
Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increase polyamine export and catabolism. In a Phase 3 clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase 3 trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP.

CPP-1X Eflornithine
CPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase 1 or Phase 2 investigatorinitiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity.

On July 19, 2023 SURGE Therapeutics (SURGE), a biotech company pioneering the delivery of immunotherapy during cancer surgery, reported the completion of a $32 million Series B financing led by Bioluminescence Ventures, with participation from KdT Ventures, Piedmont Capital, and existing investors 8VC, Alumni Ventures, Camford Capital, Cancer Research Institute, Intuitive Ventures, Khosla Ventures, and Pitango HealthTech (Press release, SURGE Therapeutics, JUL 19, 2023, View Source [SID1234633324]).

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The funding will be used to further development of the SURGE intraoperative immunotherapy approach, expand the team, and advance multiple clinical trials for its injectable biodegradable hydrogel, which may be administered during any surgical oncology procedure. In connection with the financing, Kouki Harasaki, Ph.D., Managing Partner at Bioluminescence Ventures, will join SURGE’s Board of Directors.

The company recently dosed the first two patients in a Phase 1/2a trial for its lead intraoperative immunotherapy candidate, STM-416, in patients with recurrent bladder cancer – a major unmet medical need – to improve post-resection outcomes. SURGE’s intraoperative approach enables extended, localized release of immunotherapy at the site of surgical tumor resection. This intervention may prevent tumor relapse and induce systemic antitumor immunity, potentially eliminating existing micrometastases.

"The capital that we have raised to date will allow SURGE to generate proof-of-concept event-free survival data with our lead program and advance our second and third programs through Phase 1," said Michael Goldberg, Ph.D., CEO & Founder, SURGE Therapeutics. "Intraoperative immunotherapy is a platform approach that can potentially confer clinical benefit across multiple cancer types, using different molecules. Surgery is the standard of care for most patients with solid tumors, and it is common for a small number of cancer cells to remain behind. Our mission is to ensure that nobody grieves the loss of a loved one due to preventable post-surgical cancer recurrence."

"Currently, cancer surgery is a physical intervention only. Physicians typically do not administer any kind of immunotherapy during surgical tumor resection, which we believe is a missed opportunity, as post-surgical recurrence and metastasis account for 90 percent of cancer-related deaths," said Kouki Harasaki, Ph.D., Managing Partner, Bioluminescence Ventures. "SURGE has a unique first-mover advantage in the intraoperative immunotherapy space to potentially improve patient outcomes and become the standard of care as a seamless complement to surgery. We are very excited about working with the SURGE team towards realizing this objective."

Reprogramming the body’s response to surgery from immunosuppressive to immunostimulatory may trigger the patient’s immune system to destroy both local and distal residual cancer cells, reducing recurrence and improving survival. In multiple aggressive murine models of metastasizing cancer, intraoperative immunotherapy vastly improved survival benefit relative to traditional routes of administration, whether systemic or local. Confirmation in patients could represent a major advancement in cancer care.

On July 19, 2023 Hoth Therapeutics, Inc. (NASDAQ: HOTH), a patient-focused biopharmaceutical company, reported that it has received approval from the Food & Drug Administration ("FDA") for a protocol change in its Phase 2a clinical trial of HT-001 (Press release, Hoth Therapeutics, JUL 19, 2023, https://www.prnewswire.com/news-releases/hoth-therapeutics-receives-protocol-approval-for-ht-001-cancer-therapeutic-301880450.html [SID1234633323]). Participants will apply HT-001 Gel once per day for 6 weeks, during which the effect on treating acneiform rash and other skin disorders induced by EGFRI therapy will be evaluated using different assessment tools to measure severity of rash, pain, and itching (pruritus), as well as the change in quality of life.

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The study will be completed in 2 parts: the first part is an open-label (unblinded) cohort and all patients will receive HT-001 topical gel with the active ingredient; the second part is a randomized, placebo-controlled, parallel Phase 2a dose-ranging study and patients will be randomized to receive one of three concentrations of HT-001 or placebo. Hoth will compare HT-001 to the placebo in the second period to see if HT-001 provides a significant treatment effect.

"With our recent change in protocol approved, we believe that HT-001 for the treatment of skin toxicities associated with Epidermal Growth Factor Receptor Inhibitors will be more widely available for patients suffering from chemo rash," stated Hoth Therapeutics Chief Executive Officer, Robb Knie.

More information on the trial can be found at clinicaltrials.gov.

On July 19, 2023 BioCity Biopharma, a clinical-stage biopharmaceutical company committed to developing novel and highly differentiated, modality-independent therapeutics for cancer and autoimmune disorders, reported the dosing of the first patient in a Phase 1a/1b clinical trial of its first-in-class CDH3 antibody drug conjugate (ADC), BC3195 in China (Press release, Biocity Biopharma, JUL 19, 2023, View Source [SID1234633322]). The study will assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of BC3195 in patients with locally advanced or metastatic solid tumors.

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BC3195 is a novel ADC targeting CDH3/P-cadherin, a calcium-dependent cell-cell adhesion glycoprotein highly expressed in a variety of malignancies, including lung, breast, gastric, ovarian, colorectal, and pancreatic cancers. CDH3 expression is low or undetectable in normal tissues, making it an ideal target for anticancer therapies, particularly ADCs.

Currently, BC3195 is the only ADC targeting CDH3 in clinical development globally. In preclinical studies, BC3195 binds to cell surface CDH3 with strong affinity and is efficiently internalized. BC3195 is designed with a clinically validated, cleavable linker and payload (vc-MMAE) allowing for the destruction of targeted tumor cells as well as surrounding cells which is known as the bystander effect. In animal models, BC3195 demonstrated a favorable safety profile and strong antitumor activity with tumor growth inhibition of ≥100%.

In addition to clinical trials being conducted in China, BC3195 has an active US IND. BioCity Biopharma expects to obtain preliminary clinical data on BC3195 by the end of 2023 from clinical trials in China as well as in the US.