On July 11, 2024 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, reported that it has submitted an application to the U.S. Food and Drug Administration (FDA) for Orphan Drug Designation for its drug candidate Namodenoson in the treatment of pancreatic carcinoma (Filing, 6-K, Can-Fite BioPharma, JUL 11, 2024, View Source [SID1234644789]).

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An orphan drug is defined in the 1984 amendments of the U.S. Orphan Drug Act (ODA) as a drug intended to treat a condition affecting fewer than 200,000 persons in the United States. Orphan designation qualifies the sponsor of the product for seven-year marketing exclusivity to the first sponsor obtaining FDA approval of a designated drug, a tax credit equal to 50% of clinical investigation expenses, exemption/waiver of the Prescription Drug User Fee Act (PDUFA) application filing fees, assistance in the drug development process, and Orphan Products Grant funding eligibility.

Can-Fite plans to start shortly a Phase IIa clinical study that will be a multicenter open-label trial in patients with advanced pancreatic adenocarcinoma whose disease has progressed on at least first line therapy. The trial will evaluate the safety, clinical activity, and pharmacokinetics (PK) of Namodenoson in this population. All patients will receive oral Namodenoson 25 mg administered twice daily for consecutive 28-day cycles. Patients will be evaluated regularly for safety. Approximately 20 evaluable patients will be enrolled. The primary objective of this trial is to characterize the safety profile of Namodenoson and the secondary objective is to evaluate the clinical activity as determined by the Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DoR), and Overall Survival (OS). Can-Fite has already been granted Orphan Drug Status for Namodenoson for the indication of advanced liver cancer by the FDA and also by the EMA.

"The Orphan Drug application for Namodenoson underscores the high unmet medical need for a safe and efficacious drug for this devastating disease," said Motti Farbstein, CEO of the Company. "This application further validates our belief that Namodenoson may potentially offer efficacy on top of the drug safety that has been already proved in other clinical indications. Upon marketing approval, receiving market exclusivity for Namodenoson would be significantly beneficial to Can-Fite."

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On July 11, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported its quarterly results for the month ending June 2024 (Press release, Alligator Bioscience, JUL 11, 2024, View Source [SID1234644787]).

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"This quarter we have continued to push forward with the clinical and commercial development of our robust immuno-oncology pipeline. Our lead asset mitazalimab demonstrated improved median Overall Survival at the 18-month follow-up mark, building on the impressive OPTIMIZE-1 Phase 2 top-line readout in pancreatic cancer we announced at the start of the year. Our preparations for mitazalimab’s Phase 3 are progressing well, along with our efforts to secure a commercial partnership. We were very pleased to see the Moores Cancer Center initiate its Phase 1 clinical study of mitazalimab injected intratumorally in patients with locally advanced pancreatic cancer. In fact, we have received a significant increase in interest from the scientific community on the potential evaluation of mitazalimab in a number of investigator-initiated trials in different tumor types. This is a highly encouraging sign of mitazalimab’s growing reputation as a combination therapy in pancreatic cancer whose applicability can be broadened to other indications."
Søren Bregenholt, CEO of Alligator Bioscience
BUSINESS UPDATE
Mitazalimab

On June 26, Alligator announced positive 18-month follow-up data from the OPTIMIZE-1 Phase 2 study in pancreatic cancer, demonstrating a near doubling of the 18-month survival rate to 36.2% in patients treated with mitazalimab in combination with mFOLFIRINOX, compared to 18.6% reported with FOLFIRINOX[1] alone. The data also demonstrated an increase in the updated median Overall Survival to 14.9 months, increases in both the confirmed (42.1%) and unconfirmed (54.4%) Objective Response Rate, and an unprecedented median Duration of Response of 12.6 months. These latest OPTIMIZE-1 results compare favorably to the previously reported outcomes with first line chemotherapies FOLFIRINOX[1]and NALIRIFOX[2].
On June 3, Alligator announced the publication of a scientific article entitled "Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre phase 1b/2 study" in the world-leading clinical oncology research journal, The Lancet Oncology.
On May 14, Alligator announced the initiation of an investigator-initiated Phase 1 clinical study evaluating the safety and efficacy of mitazalimab injected intratumorally at the time of surgical irreversible electroporation (IRE) in patients with locally advanced pancreatic cancer (LAPC). The study is being conducted by researchers at the Moores Cancer Center at UC San Diego (NCT06205849) and is being financed by the US National Cancer Institute.
On April 8, "Mitazalimab, a potent CD40 agonist in combination with FOLFIRINOX demonstrates changes consistent with increased immune activation in TME[3] and peripheral blood in a preclinical pancreatic cancer tumor model" was presented by Alligator at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, California.
On June 1, "CD4 effector T cell expansion to identify objective responses to the CD40 agonist mitazalimab in combination with modified FOLFIRINOX (mFFX) as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC) in the OPTIMIZE-1 study" and "OPTIMIZE-1 primary analysis: Safety, efficacy and biomarker results of a phase 1b/2 study combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC)" was presented by Alligator at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois.
On June 29, "CD40 agonist mitazalimab combined with mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Primary analysis of the OPTIMIZE-1 phase 1b/2 study" was presented by Alligator at the European Society for Medical Oncoloy Gastrointestinal conference in Münich, Germany.
ATOR-4066

On April 9, "ATOR-4066, a Neo-X-Prime bispecific antibody targeting CD40 and CEACAM5, induces tumor localized immune cell activation in preclinical in vivo tumor model" was presented by Alligator at the AACR (Free AACR Whitepaper) Annual Meeting in San Diego, California.
CD40 Publication

On May 20, Alligator announced the publication of a scientific article entitled "Next generation CD40 agonists for cancer immunotherapy" in the peer-reviewed medical journal Expert Opinion on Biological Therapy.
Exercise of development option by Orion

On April 26, Alligator announced that Orion Corporation, a global pharmaceutical company based in Finland, had selected the lead bispecific antibodies from the companies’ second development program, and was exercising its option to develop these molecules under the existing 2021 research collaboration and research agreement. The exercise of this development option triggered an undisclosed milestone payment to Alligator.
HLX22 (AC101)

On May 21, Alligator announced that Shanghai Henlius Biotech, Inc. had received Investigational New Drug (IND) clearance from the US Food and Drug Administration (FDA) to initiate a Phase 3 study to evaluate HLX22 (AC101) in combination with trastuzumab (Herceptin) and chemotherapy in 1st line HER2-positive advanced gastric cancer patients.
New Chief Financial Officer announced

On June 14, Alligator announced the appointment of Johan Giléus as the company’s new Chief Financial Officer as of August 12, 2024, to oversee financial strategy and operations.
Financing

On April 9, Alligator announced it will receive SEK 107.1 million in gross proceeds from the Preferential Rights Issue approved at the Extraordinary General Meeting held on March 14.
On June 25, Alligator announced a financing agreement with Fenja Capital worth up to SEK 80 million, providing financial and strategic flexibility and extending the company’s cash runway into the first quarter of 2025.
Significant events after the end of the period:

Mitazalimab

On July 10, Alligator announced the completion of the recruitment of the 450 μg/kg back-fill cohort to the OPTIMIZE-1 study. The additional cohort was enrolled in order to provide further dose characterization following advice from the FDA, to ensure mitazalimab Phase 3 readiness.
FINANCIAL SUMMARY FOR Q2 2024 and H1 2024
The financial summaries for the quarterly periods ending June 30th, 2024 and June 30th, 2023 are presented below.

All amounts in MSEK,
unless specified April – June 2024 April – June 2023
Net Sales 7.6 17.4
Operating profit/loss -47.4 -63.7
Profit/loss for the period -49.2 -63.7
Cash & Cash Equivalents 77.5 160.6
Cash Flow for the period 37.4 115.6
Earnings per share (SEK)
before and after dilution -0.07 -0.19
The financial summaries for the half-yearly periods ending June 30th, 2024 and June 30th, 2023 are presented below.

All amounts in MSEK,
unless specified January – June 2024 January – June 2023
Net Sales 14.6 27.0
Operating profit/loss -107.0 -125.9
Profit/loss for the period -112.0 -126.3
Cash & Cash Equivalents 77.5 160.6
Cash Flow for the period 11.3 63.4
Earnings per share (SEK)
before and after dilution -0.16 -0.46
The full report is attached as a PDF, and is also available on the company’s website: View Source

Alligator will host a conference call on Thursday, July 11, at 4:15 p.m. CEST/ 10:15 a.m. EDT for investors, analysts and media, where CEO Søren Bregenholt, CFO Marie Svensson, and CMO Dr. Sumeet Ambarkhane will present and comment on the Q2 interim report, which will be followed by a Q&A session.

On July 10, 2024 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), reported that, the Compensation Committee of Crinetics’ Board of Directors granted non-qualified stock option awards to purchase an aggregate of 137,900 shares of its common stock to eighteen new non-executive employees under the Crinetics Pharmaceuticals, Inc. 2021 Employment Inducement Incentive Award Plan (the "2021 Inducement Plan") (Press release, Crinetics Pharmaceuticals, JUL 10, 2024, View Source [SID1234644790]). The stock options were granted as inducements material to the employees entering into employment with Crinetics in accordance with Nasdaq Listing Rule 5635(c)(4).

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The 2021 Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously employees of Crinetics, or following a bona fide period of non-employment, as an inducement material to such individuals’ entering into employment with Crinetics, pursuant to Nasdaq Listing Rule 5635(c)(4). The options have an exercise price of $50.80 per share, which is equal to the closing price of Crinetics’ common stock on The Nasdaq Global Select Market on July 10, 2024. The shares subject to the stock options will vest over four years, with 25% of the shares vesting on the one-year anniversary of the applicable vesting commencement date and the balance of the shares vesting in a series of 36 successive equal monthly installments thereafter, subject to each employee’s continued employment with Crinetics on such vesting dates. The options are subject to the terms and conditions of the 2021 Inducement Plan and the terms and conditions of a stock option agreement covering the grant.

On July 10, 2024 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases and cancer, reported that the Compensation Committee of the company’s Board of Directors granted one employee a nonqualified stock option to purchase 72,000 shares of its common stock with an exercise price of $0.55 per share, which is equal to the closing price of Kezar’s common stock on July 8, 2024, the grant date of the award (Press release, Kezar Life Sciences, JUL 10, 2024, View Source [SID1234644780]). The stock option was granted as an inducement award material to the individual entering into employment with Kezar, in accordance with Nasdaq Listing Rule 5635(c)(4).

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The stock option will vest over a four-year period, with 25% of each option vesting on the first anniversary of the employee’s start date, and 1/48th of the total shares vesting monthly thereafter, subject to continued employment on each vesting date. The option is subject to the terms and conditions of Kezar’s 2022 Inducement Plan and the stock option agreement covering the grant.

On July 10, 2024 Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a late-stage biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products, reported expected milestones in the second half of calendar 2024 and recapped key achievements year-to-date (Press release, Citius Pharmaceuticals, JUL 10, 2024, View Source [SID1234644779]).

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Leonard Mazur, Chairman and CEO of Citius stated, "Our solid execution since the beginning of the year sets us up for potentially transformative catalysts in the coming months. Mino-Lok’s strong Phase 3 topline results support its potential to become part of the standard of care for treating catheter-related bloodstream infections. Mino-Lok would also have a first and only advantage in a market with no approved or investigational products for salvaging infected central venous catheters. For LYMPHIR, the FDA is currently reviewing our Biologics License Application, with an expected decision on August 13th. We are preparing for near-term commercialization of LYMPHIR if approved. These near-term catalysts should enable the company to optimize its current cash runway, future cash needs, as well as create potential non-dilutive cash opportunities.

"Our primary purpose and mission for these late-stage assets is to provide best-in-class, highly effective treatment options for patients and caregivers," Mazur added. "Ultimately, we believe our achievements and milestones offer powerful levers for value creation."

Late-Stage Assets: Mino-Lok and LYMPHIR

Citius significantly advanced its two late-stage product candidates in the first six months of 2024, and expects several key milestones in the near term.

Mino-Lok: Citius recently announced positive topline data from the Phase 3 study of Mino-Lok in catheter-related bloodstream infections (CRBSIs). Primary and secondary endpoints were met with statistical significance.
Next steps for the Mino-Lok program are to prepare a submission to the U.S. Food and Drug Administration (FDA) and schedule a Type B meeting.
LYMPHIR: In March 2024, the FDA accepted the Company’s Biologics License Application (BLA) for LYMPHIR (denileukin diftitox), an IL-2-based immunotherapy for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL).
A decision on the LYMPHIR BLA is expected on August 13, 2024, the FDA’s assigned Prescription Drug User Fee Act (PDUFA) action date. If approved, Citius is preparing for LYMPHIR commercialization in 2024.
Considered a new biologic by the FDA, LYMPHIR would potentially be eligible for 12 years of exclusivity, if approved.
In addition to the initial indication, two investigator-initiated Phase 1 studies of LYMPHIR are underway to explore how the differentiated mechanism-of-action may offer potential indications beyond CTCL. The studies are in progress at the University of Pittsburgh and the University of Minnesota.
Specialty Pharma Asset: Halo-Lido

An end of Phase 2b trial meeting with the FDA was held to discuss the positive data for Halo-Lido, a prescription strength topical for symptomatic hemorrhoid treatment. The data showed a meaningful reduction in symptom severity when compared to individual components alone.
Continuing engagement with the FDA will guide the Company’s next phase of development for Halo-Lido.
Operational Milestones

Operational achievements by Citius in the first six months of 2024 delivered additional capital and stronger levers for value creation.

Citius took steps to strengthen its capital structure in preparation for LYMPHIR commercialization, if approved. A $15 million registered direct offering was completed in April 2024, extending the Company’s cash runway.
Citius plans to merge a wholly owned subsidiary with TenX Keane Acquisition (Nasdaq: TENK) to form publicly listed company, Citius Oncology, Inc. The transaction is pending review by the U.S. Securities and Exchange Commission (SEC) and TENK shareholder approval as well as contractual and customary closing conditions.
About Mino-Lok

Mino-Lok (MLT), a novel antibiotic lock solution that combines minocycline, ethanol and edetate disodium, is designed to treat patients with catheter-related blood stream infections. Citius licensed Mino-Lok from an affiliate of The University of Texas MD Anderson Cancer Center. Mino-Lok is designed to offer an alternative to removing and replacing a central venous catheter (CVC), which may lead to a reduction in serious adverse events and cost savings to the healthcare system. If approved, Mino-Lok would be the first and only FDA-approved treatment that salvages central venous catheters that cause central line-related blood stream infections.

About LYMPHIR (denileukin diftitox-cxdl)

LYMPHIR is a recombinant fusion protein that combines the interleukin-2 (IL-2) receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. In 2011 and 2013, the FDA granted orphan drug designation to LYMPHIR for the treatment of PTCL and CTCL, respectively. In 2021, denileukin diftitox received regulatory approval in Japan for the treatment of CTCL and peripheral T-cell lymphoma (PTCL). Subsequently in 2021, Citius acquired an exclusive license with rights to develop and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia.

About Halo-Lido

Halo-Lido (CITI-002) is a proprietary topical formulation intended to provide symptomatic relief to individuals suffering from hemorrhoids. Hemorrhoids are a gastrointestinal disorder characterized by pain, swelling, itching, tenderness, and bleeding. Although hemorrhoids are not life-threatening, individual patients often suffer painful symptoms that can limit social activities and have a negative impact on the quality of life. More than half of the U.S. population will experience hemorrhoidal disease at least once in their life. Each year, nearly 10 million patients in the U.S. report symptoms.