On August 21, 2023 AskGene Pharma Inc. reported that the first patient has been dosed at Columbia University Irving Medical Center in New York City in the phase I clinical trial of ASKG915 (Press release, AskGene Pharmaceuticals, AUG 21, 2023, View Source [SID1234634595]). The study is an open label, multi-regional phase I clinical trial evaluating the safety, tolerability, and pharmacokinetics of ASKG915 as a single agent in patients with selected advanced solid tumors. ASKG915 is the first anti-PD-1/IL-15 prodrug in clinical development in the world.

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Barbara Hickingbottom, J.D., M.D., Chief Medical Officer of AskGene commented: "Cytokines are natural immune stimulants, which cannot be used widely due to their short half-lives and narrow therapeutic windows. AskGene uses its proprietary technology of SmartKine to overcome these challenges. We already have on-going clinical studies of ASKG315 (an IL-15 prodrug) and an IL-2 prodrug through a partnership. With ASKG915, we expand our platform to include a molecule that should produce both full anti-PD-1 and IL-15 effects. Such molecules may be able to treat both patients who have failed anti-PD-1 treatment, as well as those who need the extra boost of IL-15 to achieve a response to checkpoint inhibitor therapy. FIH dosing of ASKG915 is an important milestone towards making this next-generation immunotherapy available to patients in need. We are very excited about the progress made so far and look forward to the upcoming POC data from our clinical studies in the future."

About ASKB915

ASKG915 is the world’s first anti-PD-1 antibody / IL-15 prodrug fusion molecule to enter clinical development. The molecule can achieve tumor targeting through the anti-PD-1 antibody and be locally activated at the tumor site. It is also designed to allow a high enough dose so that the anti-PD-1 antibody has full PD-1 blockage functionality. Preclinical data showed that ASKG915 has extended PK, significantly better efficacy than anti-PD-1 antibody monotherapy, and an expanded therapeutic window. ASKG915 is expected to benefit patients who are not responding to current anti-PD-1 antibody therapies. A multi-regional phase I clinical trial in the US and China was started in Aug 2023.

On August 21, 2023 Amgen (NASDAQ:AMGN) reported that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) will review data supporting the supplemental New Drug Application (sNDA) for the full approval of LUMAKRAS (sotorasib) for adults with previously treated locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC) at a meeting on Oct. 5, 2023 (Press release, Amgen, AUG 21, 2023, View Source [SID1234634594]).

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LUMAKRAS/LUMYKRAS is approved in several markets outside the United States including Europe, South America, Asia and the European Union. To date, over 6,500 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use.

Lumakras has demonstrated a favorable benefit/risk profile in multiple studies in non-small lung cancer and other tumor types such as colo-rectal cancer. Amgen is progressing the largest and broadest global KRASG12C inhibitor development program exploring multiple combination regimens, with clinical trial sites spanning five continents.

"We believe in the clinical value of LUMAKRAS for prescribers and patients navigating KRAS G12C-mutated NSCLC and we look forward to discussing the comprehensive data package for LUMAKRAS with members of the Committee," said David M. Reese, M.D., executive vice president of Research and Development at Amgen.

LUMAKRAS received accelerated approval from the FDA on May 28, 2021. The sNDA for full approval of LUMAKRAS was accepted by the FDA for standard review and a Prescription Drug User Fee Act (PDUFA) target action date of Dec. 24, 2023, has been set.

About LUMAKRAS/LUMYKRAS (sotorasib)

Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.1 LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk profile with rapid, deep, and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.2

In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval with its approval in the U.S., under accelerated approval. LUMAKRAS/LUMYKRAS is also approved in the European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan, Turkey, Thailand, Qatar, Australia, Argentina, Brazil, Canada, Great Britain, Kuwait, Macao, Singapore, Mexico, Israel, Bulgaria, Hungary, Romania, and Russia. Additionally, Amgen has submitted MAAs in Colombia, Malaysia and Saudi Arabia.

LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.

About Non-Small Cell Lung Cancer and the KRAS G12C Mutation

Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.3 Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease, and 5-year survival is only 9% for those with metastatic disease.4

KRAS G12C is the most common KRAS mutation in NSCLC.5 About 13% of patients with NSCLC harbor the KRAS G12C mutation.6 The unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with other approved therapies are suboptimal, with a median progression-free survival of approximately four months following second-line treatment of KRAS G12C-mutated NSCLC.7

About CodeBreaK

The CodeBreaK clinical development program for Amgen’s drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.  

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.8 Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.2 The Phase 2 trial in metastatic colorectal cancer (mCRC) enrolled 62 patients and results have been published.9

CodeBreaK 200, the global Phase 3 multicenter, randomized, open-label, active-controlled study compared the efficacy, safety, and tolerability of sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint was progression-free survival and key secondary endpoints included overall survival, objective response rate, and patient-reported outcomes.10

CodeBreaK 300, the global Phase 3 randomized active-controlled study comparing sotorasib in combination with panitumumab to investigator’s choice (trifluridine and tipiracil, or regorafenib) in chemorefractory KRAS G12C-mutated mCRC, has completed enrollment of 160 patients. Eligible patients had KRAS G12C-mutated mCRC, received at least one prior line of therapy, and have received and progressed on or after fluoropyrimidine, irinotecan, and oxaliplatin. The primary endpoint is progression-free survival and key secondary endpoints include overall survival (OS) and objective response rate (ORR).11

Amgen also has several Phase 1b studies investigating sotorasib in combination with several other treatments across various advanced solid tumors (CodeBreaK 101) open for enrollment.12 A Phase 3 randomized controlled study will evaluate frontline sotorasib in combination with platinum doublet chemotherapy versus pembrolizumab platinum doublet combination in patients with PD-L1-negative, advanced KRAS G12C-mutated NSCLC (CodeBreaK 202).13

LUMAKRAS (sotorasib) U.S. Indication

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

LUMAKRAS (sotorasib) Important U.S. Safety Information

Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis

LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions

The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
Drug Interactions

Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS.
If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.

Please see LUMAKRAS full Prescribing Information.

On August 21, 2023 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that the European Medicines Agency (EMA) has granted Orphan Designation to its lead asset mitazalimab for the treatment of pancreatic cancer (Press release, Alligator Bioscience, AUG 21, 2023, View Source [SID1234634593]).

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Mitazalimab is a monoclonal antibody targeting CD40 designed to sensitize tumors to chemotherapy and induce immune-mediated tumor killing by activating dendritic cells, B cells, and macrophages. Mitazalimab is currently being evaluated in OPTIMIZE-1, a Phase 2 open-label, multi-center study to assess its safety and efficacy in combination with chemotherapy, mFOLFIRINOX, in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (NCT04888312).

In May 2023, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to mitazalimab for the treatment of pancreatic cancer.

"We are very pleased that the European Medicines Agency has granted orphan designation to our lead asset mitazalimab in the treatment of pancreatic cancer," said Søren Bregenholt, CEO of Alligator Bioscience. "It is our second orphan designation this year following the FDA’s decision to grant us ODD in May, meaning mitazalimab now has stronger commercial protection through market exclusivity in these two key markets. This latest designation adds to the momentum we are building in our efforts to bring this promising drug candidate to market."

To qualify for the EMA’s orphan designation, a medicine must be intended for the treatment, prevention or diagnosis of rare, life-threatening or chronically debilitating diseases that affect fewer than five in 10,000 persons in the EU. Medicines that meet these criteria are eligible for financial and regulatory incentives that include 10 years of marketing exclusivity in the EU after product approval.

In June 2023, Alligator announced a second set of strong interim results from OPTIMIZE-1, in which mitazalimab combined with mFOLFIRINOX showed deepening of tumor response and increase in objective response rate (ORR) to 57% (from initially reported 52% ORR in 23 patients) and demonstrated an interim ORR of 44% in the full study cohort (57 patients) that is expected to further improve with longer follow up. A median duration of response (DoR) of 8.7 months , as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), was also reported. This compares very strongly with an ORR of 31.6% and DOR of 5.9 months reported in a similar patient population treated with standard of care[1].

OPTIMIZE-1 is on track for top-line readout in early Q1 2024.

On August 21, 2023 Adamis Pharmaceuticals Corporation (NASDAQ: ADMP), a commercial-stage biopharmaceutical company, reported financial results for the second quarter ended June 30, 2023, and provided an update on recent corporate developments (Press release, Adamis Pharmaceuticals, AUG 21, 2023, View Source [SID1234634592]).

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Q2 2023 Corporate Highlights

· In May, the Company closed the merger with DMK Pharmaceuticals Corporation (DMK), a private, clinical-stage biotechnology company at the forefront of endorphin-inspired drug design focused on developing novel treatments for opioid use disorder and other neuro-based diseases. Ebrahim Versi, MD, PhD, CEO of DMK, was named CEO of Adamis and Chairman of the Board of Directors. David J. Marguglio, previously Chief Executive Officer of Adamis, assumed the role of President and Chief Operating Officer of the combined company. Changes to the composition of the Board of Directors were also made.

· In June, management participated in the White House Roundtable with Opioid Reversal Product Manufacturers hosted by White House Office of National Drug Control Policy Director, Dr. Rahul Gupta, White House Domestic Policy Council Advisor Neera Tanden, U.S. Assistant Secretary for Health Admiral Rachel Levine, and U.S. Assistant Secretary for Mental Health and Substance Use Dr. Miriam E. Delphin-Rittmon. While in Washington, D.C., management also met individually with 12 members and/or staff of the House of Representatives and Senate, from both parties, and discussed the opioid crisis and potential ways it could be mitigated.

· Also in June, the Company announced that its wholly owned subsidiary DMK was the recipient of a grant from the National Institute of Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) to support the development of a novel bifunctional small molecule for the treatment of alcohol use disorder.

· In July, the Company committed to an unrestricted research grant to the Leiden University Medical Center Anesthesia and Pain Research Unit, to fund a ZIMHI clinical study by Albert Dahan, MD, PhD, a world expert on opioid-induced respiratory depression, otherwise known as an opioid overdose. The objective of the work will be to assess the efficacy of the Company’s ZIMHI product compared to 4mg of intranasal naloxone, which is comparable to NARCAN, and the respective number of doses required to reverse fentanyl-induced respiratory depression.

Recent Corporate Updates

· On August 4, 2023, the Company announced the closing of a public offering of 5,930,000 units at a public offering price of $1.35, with each unit consisting of one share of common stock (or pre-funded warrant in lieu thereof) and one warrant to purchase one share of common stock. The Company received gross proceeds of approximately $8.0 million before deducting fees and other estimated offering expenses at the closing, and has received additional proceeds resulting from exercises after the closing date of some of the warrants issued in the transaction.

Q2 2023 Financial Highlights

· Revenues for the second quarter ending June 30, 2023 were $0.0 million compared to $0.0 million for the same period in 2022. Revenues were negligible in both periods because no manufacturing of commercial products occurred in the second quarter in 2023 or 2022. Revenues for the six months ending June 30, 2023 and 2022 were approximately $1.5 million and $1.2 million, respectively. The increase was due to higher manufacturing demand for ZIMHI in the first quarter of 2023 versus 2022.

· Selling, general and administrative (SG&A) expenses for the three months ending June 30, 2023 were $4.0 million compared to $4.2 million for the second quarter of 2022. SG&A expenses for the first six months ending June 30, 2023 and 2022 were $8.8 million and $7.6 million, respectively. The increase was primarily attributable to approximately $1.3 million in transaction costs associated with the DMK merger.

· Research and development (R&D) expense for the second quarter of 2023 was $0.4 million compared to $3.2 million in the second quarter of the prior year. R&D expense for the first six months of 2023 was $1.7 million, compared to $7.5 million in the same period in 2022. The decline in both periods was due to terminating the clinical development activity related to a previous product candidate.

· Net loss for the combined (continued and discontinued) operations for the second quarter of 2023 was $8.6 compared to a net loss of $8.4 million in the second quarter of 2022. The increase was primarily attributable to a charge of $6.5 million for DMK’s in-process research and development acquired in the merger. Net loss for the six months ended June 30, 2023 and 2022 was $17.5 million and $18.8 million, respectively.

· Cash and cash equivalents as of June 30, 2023, were approximately $0.6 million. Additional cash infusions subsequent to the close of the second quarter include net proceeds of approximately $1.8 million from the sale of assets related to the discontinued US Compounding operations and net proceeds of approximately $7.0 million from the Company’s equity financing transaction that occurred in August.

On August 21, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, reported two abstracts accepted for oral and poster presentation at the upcoming European Association of Nuclear Medicine (EANM) 2023 Congress, which will be held in Vienna, September 9-13, 2023 (Press release, Actinium Pharmaceuticals, AUG 21, 2023, View Source [SID1234634591]). The EANM oral presentation, reflecting the potentially paradigm changing Iomab-B SIERRA data in facilitating transplants for people with AML who are currently not considered for transplant, represents the fifth oral presentation at prestigious medical conferences globally in 2023 including TCT, EBMT, SNMMI, and EHA (Free EHA Whitepaper).

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Details of the EANM oral presentation:

Presentation Title: "Safety and dosimetry evaluation of personalized dose I131-apamistamab prior to HCT in the phase 3 SIERRA trial for patients with relapsed/refractory acute myeloid leukemia (R/R AML)"
Session: Theranostics Track – Oncology & Theranostics Committee / EARL – Featured Session: Old but Novel Techniques
Date and Time: September 10, 3:00pm CET

Details of the EANM e-poster presentation:

All e-posters will be accessible for viewing for the entirety of the conference.

e-Poster Title: Feasibility of high-dose targeted radiation with I131-apamistamab in patients with relapsed/refractory AML: Dosimetry and radiation safety experience from the phase 3 SIERRA trial
e-Poster Number: EP-0608
Session Title: C: Therapy Clinical Study -> C1 Oncological Therapy Clinical Study -> C15 Other Oncological Treatments