On June 22, 2022 OCTALFA reported that its subsidiary ORPHELIA Pharma, the French biopharmaceutical company dedicated to the development and commercialization of orphan medicines for the treatment of rare and pediatric diseases, has included the first patient in the KIMOZO French Early Access Program for the treatment of relapsed or refractory neuroblastoma (Press release, ORPHELIA Pharma, JUN 22, 2022, View Source;utm_medium=rss&utm_campaign=octalfa-announces-the-inclusion-of-the-first-patient-in-the-french-early-access-program-granted-to-its-subsidiary-orphelia-pharma-for-the-use-of-kimozo-40-mg-ml-temozolomide-oral-suspension-in [SID1234616508]).

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KIMOZO 40 mg/ml (oral suspension of temozolomide) was granted an early access pre-marketing authorization (Autorisation d’Accès Précoce, AAP) in France on March 31st, 2022 by the Haute Autorité de Santé (HAS) for the treatment of relapsed or refractory neuroblastoma in patients aged 1 to 6 years as well as patients unable to swallow temozolomide capsules.

The goal of Early Access Programs in France is to accelerate access to innovative drugs before or after Market Authorization is granted once all conditions specified in Article L.5121-12 of the French Public Health Code (Code de la Santé Publique) are met:

No appropriate treatment exists;
The treatment’s implementation cannot be postponed;
The efficacy and safety of these drugs are strongly presumed based on therapeutic trials;
These drugs are considered to be innovative, particularly when compared to a possible clinically-relevant comparator.
Full details of the early access program can be found at the Haute Autorité de Santé and the ANSM websites.

About KIMOZO 40 mg/ml

KIMOZO 40 mg/ml is a liquid, taste-masked and ready-to-use oral formulation of temozolomide developed to treat rare pediatric cancers.

In France, KIMOZO has been granted an Early Access Program, to be used as monotherapy or in combination with irinotecan or topotecan in the treatment of pediatric patients aged 1 to 6 years and in patients with incapacity to swallow capsules of temozolomide and who suffer from:

refractory high-risk neuroblastoma or presenting an insufficient response to induction chemotherapy;
relapsed high-risk neuroblastoma after at least a partial response to induction chemotherapy followed by myeloablative therapy and stem cell transplantation.
KIMOZO was developed by ORPHELIA Pharma in collaboration with Gustave Roussy.

On June 22, 2022 National Brain Tumor Society reported that the U.S. Food and Drug Administration (FDA) granted accelerated approval to a new treatment combination that will now be available as an option for certain brain tumor patients (Press release, National Brain Tumor Society, JUN 22, 2022, View Source [SID1234616328]).

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The FDA approved the combination of two oral drugs called dabrafenib (brand name: Tafinlar) and trametinib (brand name: Mekinist) for the treatment of advanced tumors that have a mutation called "BRAF V600E." The approval includes use in both adult and pediatric (older than 6 years of age) high- and low-grade glioma patients with this mutation whose tumors progressed after prior treatment.

The approval is based on the results from a number of clinical trials, which included adult and pediatric high-grade and low-grade glioma patients. Data pooled from across these trials showed that the Tafinlar-Mekinist combination successfully shrank a significant percentage of these patients’ tumors. Using a measure called "Overall Response Rate (ORR)," trials found that 33% of high-grade glioma patients responded to the combination, while 50% of low-grade glioma patients saw tumor shrinkage benefits. For the pediatric glioma patients, 25% responded to the treatment.

The BRAF V600E mutation is estimated to be prevalent in 5-15% of all low-grade gliomas (15-20% of pediatric low-grade gliomas), including 60-80% of pleomorphic xanthoastrocytomas (PXA), 20-70% of gangliogliomas, and 10% of pilocytic astrocytomas. The mutation has been identified less frequently in high-grade gliomas, including approximately 3% of glioblastomas.

"This approval will offer a much-needed new treatment option for hundreds of glioma patients with a BRAF V600E mutation," said David Arons, chief executive officer, National Brain Tumor Society. "This is very positive news for the brain tumor community and offers hope that current research and drug development efforts are beginning to yield meaningful breakthroughs for patients that currently have too few options. We thank Novartis for including both adult and pediatric glioma patients in these trials, as well as the researchers and clinicians involved, and most importantly the patients and their families that participated in the studies."

The most common side effects seen in adult patients were fever, fatigue, nausea, rash, chills, headache, hemorrhage, cough, vomiting, constipation, diarrhea, muscle and joint pain, and edema.

The most common side effects seen in pediatric patients included fever, rash, vomiting, fatigue, dry skin, cough, diarrhea, dermatitis acneiform, headache, abdominal pain, nausea, hemorrhage, and constipation.

Because the approval for this treatment was granted through the FDA’s accelerated approval pathway, the sponsor of the clinical trial, Novartis, will be required to complete confirmatory trials to verify the effectiveness of these drugs to date. According to reports, the company may already have additional evidence of effectiveness in pediatric low-grade glioma patients, including in children as young as one. Based on data presented recently at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, the Tafinlar-Mekinist combination resulted in 47% ORR versus chemotherapy (11%) and reduced the risk of progression or death by 69%. Additionally, in a separate, small subset of this trial, pediatric high-grade glioma patients treated with Tafinlar-Mekinist showed an ORR of 56.1% and generally consistent safety results.

Further buoying these results were data also presented at ASCO (Free ASCO Whitepaper) 2022 from Day One Bio of their own BRAF-targeting drug, tovorafenib (DAY101), which also showed effectiveness in relapsed pediatric low-grade glioma. We await additional future results from trials of tovorafenib (DAY101).

"Given this latest approval, and the recent data from ASCO (Free ASCO Whitepaper), NBTS strongly urges that neuro-surgical and oncology providers treating glioma patients secure for patients a test that can identify their BRAF V600E status as part of robust molecular biomarker testing informed by the 2021 World Health Organization’s reclassification of CNS tumors as a routine step that could determine which patients could benefit from these drugs," added Arons.

On June 22, 2022, Applied Therapeutics, Inc. (the "Company") reported that entered into an underwriting agreement (the "Underwriting Agreement") with SVB Securities LLC (the "Underwriter"), relating to the issuance and sale pursuant to an underwritten public offering (the "Offering") of 20,000,000 shares (the "Shares") of its common stock, par value $0.0001 per share (the "Common Stock"), 10,000,000 pre-funded warrants to purchase Common Stock in lieu of Shares (the "Pre-Funded Warrants") at an exercise price of $0.0001 per share, and accompanying warrants to purchase up to 30,000,000 shares of its Common Stock (the "Common Warrants" and together with the Pre-Funded Warrants, the "Warrants") at an exercise price of $1.00 per share (the Shares and Warrants together, the "Securities") (Filing, 8-K, Applied Therapeutics, JUN 22, 2022, View Source [SID1234616309]). Each share of Common Stock and accompanying Common Warrant was sold at a public offering price of $1.00, less underwriting discounts and commissions, and each Pre-Funded Warrant and accompanying Common Warrant was sold at a public offering price of $0.9999, less underwriting discounts and commissions, as described in the prospectus supplement, dated June 22, 2022, filed with the Securities and Exchange Commission on June 24, 2022. The Pre-Funded Warrants and the Common Warrants are immediately exercisable and will expire five years from the date of issuance. Holders may not exercise any Pre-Funded Warrants or Common Warrants that would cause the aggregate number of shares of Common Stock beneficially owned by the holder to exceed 9.99% of the Company’s outstanding Common Stock immediately after exercise. Holders of the Warrants (together with affiliates) who immediately prior to the issue date beneficially own more than 9.99% of outstanding Common Stock may not exercise any portion of their Pre-Funded Warrants or Common Warrants if the holder (together with affiliates) would beneficially own more than 19.99% of the Company’s outstanding Common Stock after exercise. The Warrants are subject to adjustment in the event of certain stock dividends and distributions, stock splits, stock combinations, reclassifications or similar events affecting the Common Stock and also upon any distributions for no consideration of assets to the Company’s stockholders. In the event of certain corporate transactions, the holders of the Warrants will be entitled to receive, upon exercise of the Warrants, the kind and amount of securities, cash or other property that the holders would have received had they exercised the Warrants immediately prior to such transaction. The Warrants do not entitle the holders thereof to any voting rights or any of the other rights or privileges to which holders of Common Stock are entitled. The Company intends to use the net proceeds from this Offering for general corporate purposes. General corporate purposes may include research and development costs, including the conduct of clinical trials and process development and manufacturing of the Company’s product candidates, expansion of the Company’s research and development capabilities, working capital and capital expenditures. Entities affiliated with Alexandria Venture Investments, LLC, which, as of March 31, 2022, owned 13.1% of the Company’s outstanding Common Stock, purchased 3,500,000 shares and 1,500,000 Pre-Funded Warrants in the Offering.

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The Offering closed on June 27, 2022.

On June 22, 2022 The Company reported that entered into a Securities Purchase Agreement (the "Blue Lake Purchase Agreement"), with Blue Lake Partners, LLC ("Blue Lake"), pursuant to which the Company issued a convertible promissory note in the aggregate principal amount of $335,000 (the ‘Blue Lake Note") (Filing, 8-K, Mateon Therapeutics, JUN 22, 2022, View Source [SID1234616285]). The Blue Lake Note is convertible into shares of the Company’s common stock, par value $0.01 per share ("Common Stock"). The Blue Lake Purchase Agreement and Blue Lake Note are part of a cumulative debt financing of $1 million through JH Darbie and Co., Inc. ("JH Darbie"), of which the Company raised $605,000 from Mast Hill Fund, LP ("Mast Hill") in May 2022.

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The Mast Hill and Blue Lake Purchase Agreements and the Mast Hill and Blue Lake Notes were entered into for aggregate gross proceeds to the Company of up to $1 million (the "Financing"), undertaken by the Company pursuant to a Finder’s Fee Agreement between the Company and JH Darbie, dated October 26, 2021 (the "Agreement"). Pursuant to the Agreement, JH Darbie will be entitled to a finder’s fee of: (a) 10% of the gross proceeds received by the Company in cash; and (b) warrants equal 10% warrant coverage of the amount raised, with a purchase price equal to the Conversion Price, with such warrants to expire five years from the date of issuance. For this Financing, JH Darbie has agreed to accept a lower cash finder’s fee of 4.5% of the gross proceeds and warrant coverage of 10%. The Blue Lake Purchase Agreement and the Blue Lake Note contain identical terms to the securities purchase agreements (and promissory notes issued thereunder), to the Mast Hill funding from May 27, 2022 (the "Prior Issuance"), except with reference to the name of the holders, the use of proceeds, which included repayment of certain debt, general corporate expenses and payroll, as applicable, and the law governing the terms of the Prior Issuance. The Prior Issuance was previously reported on our Current Report on Form 8-K filed with the Securities and Exchange Commission ("SEC") on June 3, 2022.

The Notes carry an interest rate of 12% per annum and matures on the earlier of (a) the one-year anniversary of the date of the Purchase Agreements, or (b) the acceleration of the maturity of the Notes by the applicable holder upon occurrence of an Event of Default (as defined below). The Notes contain a voluntary conversion mechanism whereby the applicable holder may convert the outstanding principal and accrued interest under the terms of the Notes into shares of Common Stock (the "Conversion Shares"), at a fixed price of $0.10 per share (the "Conversion Price"), subject to adjustments upon the occurrence of certain corporate events. The Company also issued 3,025,000 warrants to purchase shares of Common Stock of the Company at an exercise price of $0.20. Prepayment of the Notes may be made at any time upon three trading days’ prior written notice to the respective holder, by payment of the then outstanding principal amount plus accrued and unpaid interest and reimbursement of such holder’s administrative fees. The Notes contains customary events of default (each an "Event of Default"). If an Event of Default occurs, at the respective holder’s election, the outstanding principal amount of the Notes, plus accrued but unpaid interest, will become immediately due and payable in cash. The Purchase Agreements require the Company to use the proceeds for general working capital, and not for (i) the repayment of any indebtedness owed to officers, directors or employees of the Company or their affiliates, (iii) any loan to or investment in any other corporation, partnership, enterprise or other person (except in connection with the Company’s currently existing operations), (iv) any loan, credit, or advance to any officers, directors, employees, or affiliates of the Company, or (v) in violation or contravention of any applicable law, rule or regulation.

The issuance of the Notes are exempt from the registration requirements of the Securities Act of 1933, as amended ("Securities Act"), in reliance on the exemptions provided by Section 4(a)(2) of the Securities Act. The shares of Common Stock issuable upon conversion of the Notes have not been registered under the Securities Act or any other applicable securities laws, and unless so registered, may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Securities Act.

The foregoing descriptions of the Purchase Agreements and the Notes are qualified in their entirety by reference to the full text of the form of such agreements, copies of which are attached as Exhibit 10.1 and 10.2, respectively and each of which is incorporated herein in its entirety by reference.

On June 22, 2022 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported the signing of a definitive agreement for the sale of revenues from U.S. and European royalty and milestone interests in Klisyri (tirbanibulin) to Sagard Healthcare Partners and funds managed by Oaktree Capital Management, L.P. ("Oaktree") for $85 million (Press release, Athenex, JUN 22, 2022, View Source [SID1234616235]). Approximately $80 million of the proceeds from the transaction will be used toward partially paying down existing debt and operating the business, with $5 million to be placed into escrow and paid to Athenex upon the satisfaction of certain conditions. The transaction is subject to customary closing conditions.

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"We are executing on our new strategy and will continue to deliver on the objectives that we laid out to extend our cash runway by over 18 months. We are pleased to enter into this agreement, as we believe it generates meaningful benefits for our stockholders as we continue to pay down debt and extend our cash runway," said Dr. Johnson Lau, Chief Executive Officer of Athenex. "The sale of the revenues from the U.S. and European royalty and milestone interests in Klisyri represents another step in continuing to monetize non-core assets to focus on developing our potential best-in-class NKT cell platform."

Ladenburg Thalmann & Co. Inc. and Royalty/Revenue Interest Capital Advisors LLC served as financial advisors to Athenex and Cooley LLP served as legal counsel to Athenex. Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. served as legal counsel to Sagard Holdings and Oaktree.