ON December 7, 2023 Bristol Myers Squibb (NYSE: BMY) reported the Phase 3 CheckMate -8HW trial evaluating Opdivo (nivolumab) plus Yervoy (ipilimumab) compared to investigator’s choice of chemotherapy as a first-line treatment for patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) met the dual primary endpoint of progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR) at a pre-specified interim analysis (Press release, Bristol-Myers Squibb, DEC 7, 2023, View Source;8HW-Trial-Evaluating-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Compared-to-Chemotherapy-in-Microsatellite-InstabilityHigh-or-Mismatch-Repair-Deficient-Metastatic-Colorectal-Cancer-Meets-Primary/default.aspx [SID1234638231]).

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The dual immunotherapy combination of Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in PFS compared to chemotherapy. The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified.

"The benefits of Opdivo plus Yervoy in MSI-H/dMMR mCRC were established previously in CheckMate -142, in which the dual immunotherapy combination demonstrated strong and durable anti-tumor activity among patients who had progressed after prior fluoropyrimidine-based combination chemotherapy," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. "Now, with these positive results from CheckMate -8HW, we have randomized data showing Opdivo plus Yervoy significantly improved PFS in the first line setting for patients with MSI-H/dMMR mCRC. These results further support the benefits of dual PD-1 and CTLA-4 inhibition, and demonstrate our continued commitment to pursue combination strategies that may help improve outcomes for patients with high unmet need."

CheckMate -8HW is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to either Opdivo alone or investigator’s choice of chemotherapy in patients with MSI-H or dMMR mCRC. The dual primary endpoints of the trial are PFS per BICR for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. The study is ongoing to assess the other dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone, as well as secondary endpoints.

The company will complete a full evaluation of the available CheckMate -8HW data and work with investigators to share the results with the scientific community at an upcoming medical conference, as well as discuss with health authorities.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial.

About CheckMate -8HW

CheckMate -8HW is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to Opdivo alone or investigator’s choice chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).

Approximately 830 patients were randomized to receive either Opdivo monotherapy (Opdivo 240 mg Q2W for six doses, followed by Opdivo 480 mg Q4W), Opdivo plus Yervoy (Opdivo 240 mg plus Yervoy 1 mg/kg Q3W for four doses, followed by Opdivo 480 mg Q4W), or investigator’s choice of chemotherapy. The dual primary endpoints of the trial are progression-free survival (PFS) per blinded independent central review (BICR) for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. The trial also includes several secondary safety and efficacy endpoints, including overall survival (OS).

The study is ongoing to assess the second dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy, as well as secondary endpoints.

About dMMR or MSI-H Colorectal Cancer

Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease; it is the second leading cause of cancer-related deaths among men and women combined.

Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors; they are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.

On December 7, 2023 Bristol Myers Squibb (NYSE: BMY) reported that on December 6, 2023, its Board of Directors authorized the repurchase of an additional $3 billion of the company’s common stock under the company’s multi-year share repurchase program (Press release, Bristol-Myers Squibb, DEC 7, 2023, View Source [SID1234638230]).

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With this increase, the company’s total outstanding share repurchase authorization is approximately $5 billion. The program enables management to execute repurchases at its discretion.

The timing and amount of any share repurchases under the authorization will be determined at a future date by management at its discretion and based on market conditions and other considerations. Share repurchases under the authorizations may be made through a variety of methods, which may include open market purchases, pursuant to pre-set trading plans meeting the requirements of Rules 10b5-1 and 10b-18 under the Securities Exchange Act of 1934, in privately negotiated transactions, block trades, accelerated share repurchase transactions, or any combination of such methods. The program does not obligate Bristol Myers Squibb to acquire any particular amount of its common stock, and the repurchase program may be suspended or discontinued at any time at the company’s discretion.

On December 7, 2023 Avid Bioservices, Inc. (NASDAQ:CDMO), a dedicated biologics contract development and manufacturing organization (CDMO) working to improve patient lives by providing high quality development and manufacturing services to biotechnology and pharmaceutical companies, reported financial results for the second quarter and six months ended October 31, 2023 (Press release, Avid Bioservices, DEC 7, 2023, View Source [SID1234638229]).

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Highlights from the Quarter Ended October 31, 2023, and Other Events:

"Second quarter revenues were impacted by a number of factors, requiring us to decrease our revenue guidance for the 2024 full fiscal year. With these factors now behind us, we are looking ahead to the second half of the year with some optimism. This outlook is driven in part by the fact that we expect revenue growth during the second half of the fiscal year, aided by our new business bookings of $35 million during the period. While we continue to see an increase in our late-stage project portfolio, which we view as critical to our medium and longer-term growth, we were also pleased to see some encouraging signs of early-stage programs advancing during the quarter despite the challenging macro environment," stated Nick Green, president and CEO of Avid Bioservices.

"We are pleased to have closed the quarter with a higher cash balance as compared to the end of the prior quarter, and while we have seen no requirement to utilize the credit revolver put in place earlier this year, during the quarter we agreed to extend the term through calendar Q3 2024. We were also pleased to complete construction of the cell and gene therapy (CGT) facility as planned, which also coincided with the signing of our second customer for the business. The CGT business also received further industry validation through our acceptance into the California Institute for Regenerative Medicine (CIRM) Industry Resource Partner Program. With the achievement of our CGT construction milestone, Avid has completed all phases of a broad multi-year expansion, and we are now well-positioned to meet the manufacturing needs of current and future clients advancing both mammalian and CGT products. As we stand today the business has revenue generating capacity of up to approximately $400 million, supported by a record high $199 million backlog, which includes late phase programs that we anticipate will utilize a portion of this new capacity.

"Despite the challenges of the first half of fiscal 2024, our current backlog and pipeline position us well to generate cash from operations in the near term, and significant growth in the medium-term and beyond. For these reasons, we believe the second half of the year holds great promise and opportunity for Avid."

Financial Highlights and Guidance

The company is adjusting revenue guidance for full fiscal year 2024 to $137 million to $147 million, previously $145 million and $165 million.

Revenues for the second quarter of fiscal 2024 were $25.4 million, representing a 27% decrease as compared to revenues of $34.8 million recorded in the prior year period. For the first six months of fiscal 2024, revenues were $63.1 million, a 12% decrease compared to $71.4 million in the prior year period. The decrease in revenues for both periods as compared to prior year periods was primarily attributed to fewer year to date manufacturing runs, a reduction in process development services from early-stage customers, and a reduction of revenue for changes in estimated variable consideration under a contract where uncertainties have been resolved.

As of October 31, 2023, the company’s revenue backlog was $199 million, representing an increase of 35% compared to $147 million at the end of the same quarter last year. The company expects a growing portion of its backlog will extend beyond a year.

Gross margin for the three months ended October 31, 2023, was negative 18% compared to 12% for the same period in the prior year. Gross margin for the first six months of fiscal 2024 was negative 1%, compared to a gross margin of 19% for the same period during fiscal 2023. The decrease in gross margin percentage for both periods as compared to the same prior year periods was primarily driven by lower manufacturing volumes and costs related to expansions of both our capacity and our technological capabilities. This included adding staff and associated overhead, including depreciation expense, that we believe will provide critical capacity for near and medium-term growth. Margins during the three and six months ended October 31, 2023, were also impacted by the decision to defer a customer’s PPQ campaign until after our annual maintenance shutdown in the second quarter combined with a reduction of margin for changes in estimated variable consideration under a contract where uncertainties have been resolved. The decrease in gross margin for the first six months of fiscal 2024 was further impacted by a terminated project relating to the insolvency of one of our smaller customers and a delay in our ability to recognize revenues of a customer product pending the implementation of a process change. Excluding all of these factors, our second quarter and our year-to-date adjusted gross margin would have been two percentage points and one percentage point lower than the reported gross margin in the same prior year periods, respectively.

Selling, general and administrative (SG&A) expenses for the second quarter of fiscal 2024 were $6.6 million, a decrease of 4% compared to $6.8 million recorded for the second quarter of fiscal 2023. The decrease in SG&A for the second quarter was primarily due to a decrease in payroll and other benefit expenses and other professional fees. SG&A expenses for the first six months of fiscal 2024 were $12.8 million, a decrease of 3% compared to $13.2 million recorded in the prior year period. The decrease in SG&A for the six months was primarily due to a decrease in legal, accounting and other professional fees.

During the second quarter of fiscal 2024, the company’s net loss was $9.5 million or $0.15 per basic and diluted share, compared to a net loss of $1.2 million or $0.02 per basic and diluted share for the second quarter of fiscal 2023. For the first six months of fiscal 2024, the company recorded a net loss of $11.6 million or $0.18 per basic and diluted share, as compared to net income of $0.4 million or $0.01 per basic and diluted share, during the same prior year period.

Avid reported cash and cash equivalents on October 31, 2023, of $31.4 million, compared to $38.5 million on April 30, 2023. The second quarter cash and cash equivalents balance represents a 26% increase compared to $24.9 million at the end of the first quarter of fiscal 2024.
More detailed financial information and analysis may be found in Avid Bioservices’ Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today.

Recent Corporate Developments

The company’s commercial team signed multiple new orders during the second quarter of fiscal 2024, totaling approximately $35 million net, and resulting in a record high backlog of $199 million. These orders span process development to commercial manufacturing, including cell and gene therapy services. While the majority of these new orders continue to be later-stage projects, we were pleased to see a return of early-stage projects in the mix during the quarter. We will continue to pursue projects at every stage of development in order to maintain a diversified pipeline.

During the quarter, Avid completed construction of the company’s CGMP manufacturing suites within its new, world-class cell and gene therapy (CGT) development and CGMP manufacturing facility, as scheduled. The newly launched CGMP manufacturing suites are currently undergoing final environmental monitoring and performance qualification. With the completion of this latest and final expansion project, Avid estimates that its combined facilities now have a total revenue generating capacity of up to approximately $400 million annually. Avid plans to commemorate the completion of the CGT facility by hosting a celebratory grand opening in January 2024.

Subsequent to quarter end, Avid entered into an industry partnership with the California Institute for Regenerative Medicine (CIRM), which the company believes will further strengthen its presence broadly among CDMOs, and more specifically as a manufacturer of cell and gene therapy products. With $5.5 billion in funding and more than 161 active stem cell programs in its portfolio, CIRM is dedicated to the advancement of manufacturing for adeno-associated adenovirus, as well as other cell and gene therapy programs within the state of California. Under terms of the partnership, Avid has joined the CIRM Industry Resource Partner Program to provide development and CGMP manufacturing services to CIRM-funded programs. The company will assist CIRM’s partners in accelerating gene therapy development and manufacturing through its suite of CDMO services, which span process and analytical development, cell banking, virus banking, drug substance manufacturing, and fill-finish activities. CIRM-funded programs will be offered access to Avid’s services in order to reduce the timelines required to advance through clinical development. All partnership activities will be performed in Avid’s recently launched, world-class CGT CGMP manufacturing facility.

As previously reported, on March 14, 2023, the company entered into a credit agreement (the "Credit Agreement") with certain guarantors, certain lenders and Bank of America, N.A., as administrative agent and letter of credit issuer. The Credit Facility was initially set to mature on March 13, 2024. On October 27, 2023, the company entered into an amendment to this Credit Agreement extending the maturity date to October 2024. This amendment also included a change to the applicable interest rate applied to loans under the credit facility and increased the aggregate amount of indebtedness the company can incur at any one time for fixed or capital assets. The other material terms of the Credit Agreement remained unchanged. While the company has no current plans to draw down on this facility, Avid views this instrument as a valuable short-term tool.

On December 7, 2023 AbelZeta Pharma, Inc. ("AbelZeta" or the "Company"), a global clinical-stage biopharmaceutical company focused on the discovery and development of innovative cell therapies for cancer, inflammatory and immunological diseases, reported an agreement with AstraZeneca to co-develop C-CAR031, an autologous, armored GPC3-targeting chimeric antigen receptor T Cells (CAR-T) therapy, in hepatocellular carcinoma (HCC) (Press release, AbelZeta, DEC 7, 2023, View Source [SID1234638228]). C-CAR031 is based on a novel GPC3-targeting CART (AZD5851) designed by AstraZeneca using their transforming growth factor-beta receptor II (TGFβRII) dominant negative armoring discovery platform, and is manufactured by AbelZeta in China.

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HCC is one of the most common cancers and major causes of cancer deaths in China1 , with 466 thousand new cases each year, accounting for about 50% of the total global new cases. Approximately 45% of deaths worldwide from HCC occur in greater China.2

Under the terms of the agreement, AbelZeta will receive an upfront payment from AstraZeneca for the codevelopment and commercialization of C-CAR031 in China. AbelZeta is also eligible to receive milestone payments and royalties for the global development of AZD5851, which is being solely developed, manufactured and commercialized by AstraZeneca outside of China.

At AACR (Free AACR Whitepaper) 2023, the Company presented preliminary safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) data from an investigator-initiated trial (IIT) in China showing promising anti-tumor activity and robust PK/PD profiles for C-CAR031 in patients with advanced HCC.

"We are pleased to collaborate with AstraZeneca in pursuing this novel CAR-T treatment for solid tumors," said Tony (Bizuo) Liu, Chairman and CEO of AbelZeta. "The treatment of advanced HCC has always been a great challenge, and I believe this CAR-T therapy has the potential to redefine therapeutic paradigms in HCC and other GPC3-expressing solid tumors."

Mark Cobbold, Vice President, Head Cell Therapy, Oncology R&D, AstraZeneca said: "This agreement with AbelZeta accelerates the investigation of our innovative armoring CAR-T platform in solid tumors and advances our ambition to bring novel cell therapies to more people living with hard-to-treat cancers."

About HCC
Liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide. 3,4 Several types of primary liver cancer occur in adults, HCC being the most common form. About 75% of all primary liver cancers in adults are HCC.3 Liver cancers are categorized based on the originating cell type. Hepatocellular carcinoma begins in the liver as either a single tumor or several small nodules and at this local stage can be treated by locally targeted or surgical methods. However, most patients are diagnosed at advanced-stage, or their disease progresses to advanced-stage HCC when the prognosis is poor, with a 5- year survival rate of only 7% and a median survival of ~20 months.

On December 6, 2023 ImmunoPrecise Antibodies Ltd. ("ImmunoPrecise" or "IPA" or the "Company") reported that it has priced its underwritten public offering of 1,100,000 common shares at a public offering price of $1.00 per share (Press release, ImmunoPrecise Antibodies, DEC 6, 2023, View Source [SID1234638400]). All common shares in the underwritten public offering are to be sold by the Company. The Company expects the aggregate gross proceeds from this offering, to be approximately $1.1 million, before deducting the underwriting discount and other estimated offering expenses. The Company has granted the underwriters a 30-day option to purchase up to 165,000 additional common shares. The Company expects to close the offering on December 8, 2023, subject to customary conditions.

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The Company intends to use the net proceeds from the proposed offering for research and development; capital expenditures, including expansion of existing laboratory facilities; and working capital and general corporate purposes.

The Benchmark Company is acting as the sole Book-Running Manager and. R.F. Lafferty, Inc. is acting as Co-Manager for the offering.

The securities will be offered and sold pursuant to a shelf Registration Statement on Form F-3 (File No. 333-273197) that was declared effective by the United States Securities and Exchange Commission (the "SEC") on July 14, 2023. A preliminary prospectus supplement and accompanying prospectus describing the terms of the offering has been filed with the SEC on its website at www.sec.gov. A final prospectus supplement and accompanying prospectus describing the terms of the offering will be filed with the SEC and will be available on its website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained by contacting The Benchmark Company, LLC, 150 East 58th St., 17th Floor, New York, NY 10155, by telephone at 212-312-6700 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in Canada or any other state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.