On March 20, 2023 Exelixis, Inc. (Nasdaq: EXEL) reported that the company’s Board of Directors has authorized the repurchase of up to $550 million of the company’s common stock before the end of 2023 (Press release, Exelixis, MAR 20, 2023, View Source [SID1234629044]).

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The timing and amount of any share repurchases under the share repurchase program will be based on a variety of factors, including ongoing assessments of the capital needs of the business, alternative investment opportunities, the market price of Exelixis’ common stock and general market conditions. Share repurchases under the program may be made from time to time through a variety of methods, which may include open market purchases, in block trades, accelerated share repurchase transactions, exchange transactions, or any combination of such methods. The program does not obligate Exelixis to acquire any particular amount of its common stock, and the share repurchase program may be modified, suspended or discontinued at any time without prior notice.

On March 20, 2023 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported that an independent Data and Safety Monitoring Board (DSMB) has completed an interim data review for the first cohort of patients in the Company’s ongoing Phase I/II clinical trial of Allocetra in patients with advanced-stage peritoneal metastasis arising from solid tumors as an add-on to the standard of care (SoC) chemotherapy administered via Pressurized Intraperitoneal Aerosol Chemotherapy (clinicaltrials.gov Identifier: NCT05431907) (Press release, Enlivex Therapeutics, MAR 20, 2023, View Source [SID1234629043]). The Israeli Ministry of Health (IMOH) also reviewed the interim data and provided regulatory clearance to continue the study and open the study’s next cohort. In addition, the safety profile supported a protocol amendment to start new patients in the second cohort with higher initial doses of Allocetra. This IMOH clearance follows a previously-reported IMOH clearance to the Company’s second Phase I/II clinical trial, which is evaluating Allocetra as monotherapy and in combination with anti-PD1 checkpoint inhibitors in patients with advanced-stage solid tumors

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The DSMB based its review on available safety data for the three enrolled patients in the first cohort, in which two patients received three escalating doses of Allocetra, and one received two escalating doses of Allocetra, once every six weeks as an add-on to SoC chemotherapy delivered to the peritoneum. The primary purpose of the dosing regimen for the first cohort was to establish a safety profile that may enable an increase in the Allocetra dosing level administered to additional patients in the study and potentially associate dose levels with indications of effect

There were no mortalities nor DSMB-identified safety signals in the first cohort, and the DSMB recommended that the study continue to further dose escalation and additionally agreed to increase the starting dose of Allocetra in the next cohort. Following the DSMB recommendation, the IMOH reviewed the available safety data for the first cohort and provided regulatory clearance to initiate the recruitment of patients into the second cohort

Einat Galamidi, MD, Medical Vice President of Enlivex, commented, "We are delighted with the safety profile of Allocetra when administered directly into the peritoneal cavity, as demonstrated in the first three patients in this trial. This is the first time Allocetra has been injected locally into the peritoneum cavity, a route of administration that may be relevant to various alternatives of local administration of Allocetra in different oncological indications

ABOUT THE PHASE I/II TRIAL

The Phase I/II trial is a Company-sponsored, open-label, dose escalation and expansion trial that is expected to enroll a total of approximately 12 patients across four cohorts. It is designed to evaluate the safety and potential preliminary efficacy of Allocetra combined with SoC chemotherapy in patients with peritoneal metastases arising from solid cancer. The study begins with two cohorts of intra-patient and intra-cohort dose escalation to determine the maximum feasible dose (MFD) of Allocetra in this population, followed by two additional cohorts comparing administration of Allocetra at the selected dose either before or after administration of SoC via a pressurized intraperitoneal aerosol chemotherapy procedure (PIPAC; a technique applied when patients are not eligible to receive the standard treatment due to a considerable tumor load, large quantities of persistent ascites, or other circumstances).

Intraperitoneally delivered Allocetra and SoC chemotherapy administered via PIPAC will be given to patients every six weeks. Systemic chemotherapy will also be administered per the treating oncologist’s plan. The primary endpoint is the number and severity of Allocetra-related adverse events and serious adverse events during the 16-week assessment period, starting from the first administration of study treatment. Secondary endpoints include efficacy assessments, such as best overall response rate, progression-free survival, and overall survival. Changes from baseline in macrophage and immune cell characteristics in peritoneal fluid and tissues will also be assessed as an exploratory endpoint

ABOUT ALLOCETRA

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On March 20, 2023 Century Therapeutics presented its corporate presentation (Press release, Century Therapeutics, MAR 20, 2023, View Source [SID1234629042]).

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On March 20, 2023 BioNTech SE (Nasdaq: BNTX, "BioNTech") and OncoC4, Inc. ("OncoC4"), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel biologicals for cancer treatment, reported that they have entered into an exclusive worldwide license and collaboration agreement to develop and commercialize OncoC4’s next-generation anti-CTLA-4 monoclonal antibody candidate, ONC-392, as monotherapy or combination therapy in various cancer indications (Press release, BioNTech, MAR 20, 2023, View Source [SID1234629041]). The transaction is expected to close in the first half of 2023, subject to customary closing conditions and regulatory clearances.

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CTLA-4 is a molecule that inhibits the activity of immune cells via various mechanisms. OncoC4’s CTLA-4 antibody candidate ONC-392 aims to delete immunosuppressive T cells (regulatory T cells, "Tregs") in the tumor microenvironment, but spare Tregs in healthy tissues. With a potentially differentiated safety profile, ONC-392 may be able to achieve a more effective dosing regimen in the clinic and more successful tumor killing. Data from the ongoing Phase 1/2 trial (NCT04140526) in patients with advanced solid tumors were presented at SITC (Free SITC Whitepaper) in 2022 and 2021, where ONC-392 showed encouraging clinical activity, either as single agent or in combination with pembrolizumab in patients with metastases, particularly those who progressed on immunotherapies targeting PD-1 and CTLA-4.

ONC-392 received Fast Track designation from the U.S. Food and Drug Administration ("FDA") as a monotherapy for immunotherapy-resistant non-small cell lung cancer ("NSCLC"). The data in monotherapy of PD-1-resistant NSCLC support the initiation of a randomized Phase 3 trial which will evaluate ONC-392 as monotherapy against the current standard of care in that indication (NCT05671510). The candidate is currently also being evaluated in an additional Phase 2 trial as a combination therapy with pembrolizumab in platinum-resistant ovarian cancer (NCT05446298).

"Despite being a prime target for more than a decade, we believe that targeting CTLA-4 has not reached its full potential in cancer immunotherapy," said Prof. Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech. "The data presented by OncoC4 on their ONC-392 antibody indicate a differentiated safety profile and encouraging clinical activity in various types of tumors. We believe that this antibody is a valuable addition to our immuno-oncology portfolio, whether used alone or in combination with our personalized immunotherapies."

"Because of its specific mechanism of action, we believe ONC-392 has the potential to broaden the reach of CTLA-4-targeting immunotherapy," said Yang Liu, PhD, Co-Founder, CEO and Chief Scientific Officer of OncoC4. "We very much look forward to working hand-in-hand with BioNTech in developing ONC-392 for cancer indications with unmet medical needs."

Under the terms of the agreement, OncoC4 will receive a $200 million upfront payment and is eligible to receive development, regulatory and commercial milestone payments as well as double-digit tiered royalties. BioNTech and OncoC4 will jointly develop ONC-392 as monotherapy and in combination with anti-PD-(L)-1 antibodies in a range of solid tumor indications, including NSCLC, until approval, with the parties equally sharing development costs for such studies. All combinations outside of PD-1 inhibition, in particular all combinations with a compound in BioNTech’s pipeline, will be solely developed by BioNTech. BioNTech will hold the exclusive worldwide commercialization rights for any of these products with participation of OncoC4 in certain markets to be negotiated in the future.

About ONC-392 and CTLA-4
ONC-392 is OncoC4’s next-generation anti-CTLA-4 antibody candidate. The immune checkpoint receptor CTLA-4 inhibits T cell immune response and reduces the activity of T cells in recognizing and eliminating cancer cells. Blocking CTLA-4 preserves T cell activity and enhances anti-tumor activity. OncoC4’s next-generation anti-CTLA-4 antibody candidate ONC-392 was designed to preserve CTLA-4 recycling and thus Treg function in the peripheral tissues. This aims to give rise to fewer immune-related adverse effects and a positive safety profile.

On March 20, 2023 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 a corporate and financial update for the fourth quarter and full year ended December 31, 2022 (Press release, Athenex, MAR 20, 2023, View Source [SID1234629040]).

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"In 2022, we focused on executing our strategic vision to advance our differentiated NKT cell therapy platform and reported positive clinical data for our two lead investigational CAR-NKT cell therapy products in both neuroblastoma and non-Hodgkin lymphoma," said Dr. Johnson Lau, Chief Executive Officer of Athenex. "In addition, we made significant progress in monetizing company assets during the year, in line with our planned strategy. In 2023, we are pursuing a broader range of strategic alternatives while remaining focused on improving our balance sheet as we continue to advance our promising clinical development programs."

Fourth Quarter 2022 and Recent Business Highlights

Corporate Updates:

Closed the sale of China API business
Ended the manufacturing of 503B sterile compounded products and will exit the market in April 2023
Effected a 20:1 reverse stock split of Athenex common stock on February 15, 2023; the Company received notice on March 16, 2023 that it regained compliance with Nasdaq’s continued listing requirements
Clinical Development Programs:

NKT Cell Therapy Platform

KUR-501: Autologous GD2 CAR-NKT cell therapy for relapsed/refractory high-risk neuroblastoma (R/R HRNB)

Recent FDA-imposed clinical hold of the KUR-501 Investigational New Drug Application (IND) following the death of a young heavily pretreated male patient with R/R HRNB treated at the fifth dose level of 300 million cells/m2 approximately three weeks after CAR-NKT cell therapy product administration. Baylor College of Medicine (BCM), the IND holder, continues to investigate the etiology and pathogenesis of this event
Subject was found to have human metapneumovirus infection, then Grade 1 cytokine release syndrome (CRS) that was treated with immunosuppressants
Subject later developed polyclonal hyperleukocytosis complicated by multiorgan dysfunction without evidence of sepsis
BCM is devising a safety risk mitigation plan to reopen the clinical trial, one that could include excluding patients with concomitant viral infections, but can provide no assurances that the clinical hold will be lifted or when it will be lifted. The Company is working closely with BCM to help address the FDA’s questions and remains committed to the continued safe clinical development of what it believes is a promising new CAR-NKT cell therapy product for a high unmet medical need in a pediatric orphan indication.

Anticipated Upcoming Milestones

Targeting Phase 1 GINAKIT2 study of KUR-501 reopening mid-2023, pending FDA potentially lifting clinical hold
Phase 1 GINAKIT2 dose escalation study safety and preliminary efficacy data update anticipated in 2H 2023
KUR-502: Allogeneic CD19 CAR-NKT cell therapy for relapsed/refractory B-cell malignancies

Ongoing multicenter expansion of Phase 1 dose-escalation study (ANCHOR2) initiated in Q4 2022
Anticipated Upcoming Milestones

Next clinical trial data update from the ongoing ANCHOR and ANCHOR2 studies anticipated in 2H 2023
KUR-503: Allogeneic GPC3 CAR-NKT cell therapy for previously treated advanced GPC3-expressing hepatocellular carcinoma

Anticipated Upcoming Milestones

IND application filing for the investigational treatment of adults with previously treated advanced GPC3-expressing hepatocellular carcinoma planned in 2024
Oral Paclitaxel and Encequidar

Graduation of Oral Paclitaxel combination regimen (encequidar, a PD-1 inhibitor, and carboplatin) in the neoadjuvant triple-negative breast cancer treatment subgroup of the I-SPY2 Phase 2 trial
Received marketing authorization denial from MHRA for the treatment of metastatic breast cancer based solely on chemistry, manufacturing and controls (CMC) issues
Anticipated Upcoming Milestones

Plan to discuss the I-SPY 2 Phase 2 trial data with the FDA in connection with the New Drug Application (NDA) of Oral Paclitaxel for metastatic breast cancer
Data update from I-SPY 2 Phase 2 trial for Oral Paclitaxel regimen in the neoadjuvant breast cancer treatment setting anticipated at upcoming national meetings in 2Q 2023 by Quantum Leap Healthcare Collaborative
Expecting independent panel review of MHRA decision
Specialty Pharmaceutical Business:

Athenex Pharmaceutical Division (APD) currently markets a total of 39 products with 74 SKUs
Fourth Quarter and Full Year 2022 Financial Highlights

Revenues from product sales from continuing operations increased to $21.8 million for the three months ended December 31, 2022, from $17.1 million for the three months ended December 31, 2021, an increase of $4.7 million or 27%. Product sales for the full year 2022 were $90.9 million, up from $68.5 million in 2021, which represents a 33% increase. This increase is attributed to the launch of two additional APD products, contributing $11.6 million in net product sales, and increased demand for three FDA shortage products, contributing $12.0 million in net product sales, during the full year 2022.

License fees and other revenue for the three months and year ended December 31, 2022 were $3.3 million and $11.9 million, respectively, compared to $0.8 million and $26.9 million, respectively, for the same periods in 2021.

Cost of sales for the three months ended December 31, 2022 totaled $18.2 million, an increase of $2.5 million, or 16%, as compared to $15.7 million for the three months ended December 31, 2021. Cost of sales totaled $76.1 million for the full year in 2022, an increase of 21% as compared to $62.9 million for the full year in 2021. The increase in our cost of specialty product sales was a result of the increase in sales volumes.

R&D expenses totaled $16.4 million for the three months ended December 31, 2022, down $2.0 million, or 11%, from $18.4 million for the three months ended December 31, 2021. R&D expenses totaled $51.8 million for the full year in 2022, a decrease of 33% as compared to $77.7 million for the full year in 2021. This decrease is primarily due to a decrease in costs related to Oral Paclitaxel, clinical operations, and drug licensing costs.

SG&A expenses totaled $7.2 million for the three months ended December 31, 2022, a decrease of 33% as compared to $10.8 million for the three months ended December 31, 2021. SG&A expenses totaled $44.9 million for the full year in 2022, a decrease of 30%, as compared to $64.2 million for the full year in 2021. This decrease was primarily due to a $11.5 million decrease of Oral Paclitaxel pre-launch expenses, and a decrease from the change in fair value of contingent consideration related to the Kuur Therapeutics acquisition.

The Company recorded impairment of $0.1 million related to the balance of a subsidiary’s in-process research and development during the year ended December 31, 2022, and goodwill impairment of $41.0 million during the three months and year ended December 31, 2021, based on the results of a quantitative goodwill impairment test for our reporting units.

Interest expense totaled $10.8 million and $5.0 million for the three months ended December 31, 2022 and 2021, respectively. Interest expense for the year ended December 31, 2022 totaled $25.8 million, an increase of $5.2 million, as compared to $20.7 million for the year ended December 31, 2021, primarily due to interest recognized on the royalty financing liability, partially offset by decreased borrowings on the Senior Credit Agreement with Oaktree.

Loss on extinguishment of debt amounted to $1.7 million and $3.1 million for the three months and year ended December 31, 2022, respectively. This loss was related to the prepayments we made to Oaktree on the Senior Credit Agreement during 2022.

Income tax (expense) benefit for the three months ended December 31, 2022 amounted to $0.3 million, compared to income tax expense of ($16.0) thousand for the same period in 2021. Income tax expense totaled ($0.3) million and income tax benefit totaled $10.6 million for the full year in 2022 and 2021, respectively. The income tax expense for the full year 2022 is related to foreign income tax withholdings and the income tax benefit for the full year 2021 was primarily the result of deferred taxes related to the acquisition of Kuur’s in-process research and development.

Net losses attributable to Athenex for the three months and year ended December 31, 2022 were $34.2 million and $103.4 million, respectively, or ($4.28) and ($15.81) per diluted share, respectively, as compared to a net loss of $104.4 million and $199.8 million, or ($19.08) and ($38.44) per diluted share, for the same periods in 2021. On February 15, 2023, the Company effected a 20:1 reverse stock split, and all share and per share amounts, and exercise prices of stock options, warrants, and pre-funded warrants, if applicable, in the consolidated financial statements and notes thereto have been retroactively adjusted for all periods presented to give effect to this reverse stock split.

Revenue from product sales from continuing and discontinued operations were $115.6 million and $92.3 million for 2022 and 2021, respectively, an increase of $23.3 million, or 25%. These amounts include revenues from the 503B business of $23.3 million and $19.8 million in 2022 and 2021, respectively, and revenues from the China API business of $1.4 million and $4.0 million in 2022 and 2021, respectively. The 503B business and China API business are now categorized as discontinued operations.

For further details on the Company’s financial results, including the results for the full year ended December 31, 2022, refer to the Form 10-K filed with the SEC.

Liquidity and Capital Resources Update

As of December 31, 2022, the Company had cash and cash equivalents, restricted cash, and short-term investments of $36.7 million. The Company is implementing cost savings programs and plans to monetize assets and raise capital in order to extend cash runway in 2023.

On March 7 and March 13, 2023, the Company received notices of certain alleged defaults and reservations of rights from Oaktree relating to the Senior Credit Agreement. The alleged defaults relate to (i) the Company exceeding the $10.0 million threshold for incurring additional indebtedness by having accounts payable owed to counterparties overdue by more than 90 days, (ii) the Company’s obligation to provide notice to Oaktree related to the foregoing, and (iii) the Company’s obligation to provide notice to Oaktree regarding the recent reverse stock split. Upon the occurrence of an Event of Default, Oaktree has the right to accelerate all amounts outstanding under the Senior Credit Agreement, in addition to other remedies available to it as a secured creditor of ours. If Oaktree accelerates the maturity of the indebtedness under the Senior Credit Agreement, we do not have sufficient capital available to pay the amounts due on a timely basis, if at all, and there is no guarantee that we would be able to repay, refinance or restructure the payments due under the Senior Credit Agreement. The Company responded to Oaktree, which included grounds upon which the Company disputes each of the alleged defaults. The Company has not reached a mutual agreement with Oaktree on this matter.

Athenex management will not host a conference call to accompany this release but intends to provide material updates when appropriate.