On October 30, 2023 Bristol Myers Squibb (NYSE: BMY) reported that it has priced a public offering (the "Offering") of senior unsecured notes in a combined aggregate principal amount of $4.5 billion (collectively, the "Notes") (Press release, Bristol-Myers Squibb, OCT 30, 2023, View Source [SID1234636434]). The Notes will be issued in four tranches: (i) $1,000,000,000 in aggregate principal amount of 5.750% notes due 2031, (ii) $1,000,000,000 in aggregate principal amount of 5.900% notes due 2033, (iii) $1,250,000,000 in aggregate principal amount of 6.250% notes due 2053, and (iv) $1,250,000,000 in aggregate principal amount of 6.400% notes due 2063. Bristol Myers Squibb expects that the closing of the Offering will occur on November 13, 2023, subject to the satisfaction of customary closing conditions.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Bristol Myers Squibb intends to use the net proceeds of the Offering for general corporate purposes, including, but not limited to, the financing of the previously announced proposed acquisition of Mirati Therapeutics, Inc. (the "Acquisition") and the fees and expenses in connection therewith and with the Offering. The Offering is not conditioned upon the consummation of the Acquisition.

Morgan Stanley & Co. LLC, Barclays Capital Inc., Citigroup Global Markets Inc., and J.P. Morgan Securities LLC are acting as joint book-running managers for the Offering.

The Offering of the Notes is being made pursuant to an effective shelf registration statement (including a prospectus and preliminary prospectus supplement) (File No. 333-261623) filed with the U.S. Securities and Exchange Commission (the "SEC"). You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, Bristol Myers Squibb, any underwriter or any dealer participating in the Offering will arrange to send you the prospectus and the preliminary prospectus supplement (or, if available, the prospectus supplement) if you request it by contacting Bristol Myers Squibb Investor Relations or Morgan Stanley & Co. LLC, Attn: Prospectus Department, 180 Varick Street, 2nd Floor, New York, N.Y. 10014, or by email at [email protected], Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, N.Y. 11717, by telephone at 1-888-603-5847, or by email at [email protected], Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, N.Y. 11717, by telephone at 1-800-831-9146, or by email at [email protected], or J.P. Morgan Securities LLC, Attn: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, N.Y. 11717, or by telephone at 1-866-803-9204.

On October 30, 2023 Bristol Myers Squibb (NYSE: BMY) reported that the European Medicines Agency (EMA) has validated its type II variation application for Opdivo (nivolumab) in combination with cisplatin-based chemotherapy as a first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma, based on results from the Phase 3 CheckMate -901 trial (Press release, Bristol-Myers Squibb, OCT 30, 2023, View Source [SID1234636433]). Validation of the application confirms the submission is complete and begins the EMA’s centralized review procedure.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We know that approximately 20% to 25% of patients diagnosed with urothelial carcinoma will experience disease metastasis, and an additional 5% of patients present de novo with metastatic disease. As a result, first-line treatment options that may offer these patients a chance for durable responses and improved survival outcomes are needed," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, genitourinary cancers, Bristol Myers Squibb. "We are pleased that the CheckMate -901 trial has displayed potential for Opdivo in combination with cisplatin-based chemotherapy to help address this unmet need and provide hope for patients and their loved ones. We are eager to continue working with the European Medicines Agency to discuss how we may bring this first-line regimen to appropriate patients across Europe."

In the CheckMate -901 study, the first Phase 3 trial with an immunotherapy-based combination to show statistically significant and clinically meaningful survival benefit over standard-of-care cisplatin-based chemotherapy in the treatment of this patient population, Opdivo in combination with cisplatin-based chemotherapy followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR). The safety profile was tolerable and consistent with the known safety profiles of the individual components of the regimen. No new safety concerns have been identified. The OS and PFS data from CheckMate -901 were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023.

Opdivo and Opdivo-based combinations have shown significant improvements in OS in Phase 3 clinical trials across multiple tumors, including metastatic urothelial carcinoma, advanced renal cell carcinoma, non-small cell lung cancer, malignant pleural mesothelioma, metastatic melanoma and esophageal squamous cell carcinoma.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -901 clinical trial.

About CheckMate -901
CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy or Opdivo in combination with cisplatin-based chemotherapy followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated unresectable or metastatic urothelial cancer.

In the CheckMate -901 study, evaluating Opdivo with cisplatin-based chemotherapy vs. standard-of-care chemotherapy, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin-based chemotherapy every 3 weeks followed by 480 mg/Q4 Opdivo monotherapy until disease progression or death up to a maximum of two years or chemotherapy alone. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS). The study is ongoing to assess Opdivo plus Yervoy vs. standard-of-care chemotherapy.

The OS and PFS outcomes for patients who are eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.

About Urothelial Carcinoma
Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but approximately 50% of patients who undergo surgery will experience disease progression and recurrence within two-to-three years post-surgery. Approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease. The poor durability of responses seen with chemotherapy alone in the first-line setting presents a major challenge in the treatment of metastatic disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.

On October 30, 2023 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported that it has entered into an agreement to sell a Rare Pediatric Disease Priority Review Voucher (PRV), if received, in connection with the potential approval of lovotibeglogene autotemcel (lovo-cel) for sickle cell disease (Press release, bluebird bio, OCT 30, 2023, View Source [SID1234636432]). Under the terms of the agreement, rights to the PRV will transfer to the buyer and the Company will receive $103 million upon closing of the sale, which is contingent upon the U.S. Food and Drug Administration’s (FDA’s) approval of the biologics license application (BLA) for lovo-cel and granting of the PRV.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company’s BLA for lovo-cel was previously accepted for priority review by the FDA for patients with sickle cell disease ages 12 and older who have a history of vaso-occlusive events (VOEs) and has a Prescription Drug User Fee Act (PDUFA) goal date of December 20, 2023. bluebird may be eligible for a PRV should lovo-cel be approved for patients under the age of 18.

"The potential sale of a priority review voucher would provide an important source of non-dilutive capital for bluebird ahead of the anticipated launch of lovo-cel," said Chris Krawtschuk, chief financial officer, bluebird bio. "As the FDA completes its review of lovo-cel, our team remains confident in the robustness and maturity of our BLA package for individuals 12 and older with sickle cell disease and looks forward to a regulatory decision by the end of this year."

Closing of the transaction remains subject to the approval of lovo-cel and receipt of a PRV from the FDA, as well as customary closing conditions.

About the Rare Pediatric Disease Priority Review Voucher Program

The Rare Pediatric Disease Priority Review Voucher Program is intended to encourage development of new drug and biological products for the prevention and treatment of certain rare pediatric diseases. Under this program, upon approval, the US Food and Drug Administration awards priority review vouchers to sponsors of rare pediatric disease product applications that meet certain criteria. The voucher can be redeemed to receive priority review of a subsequent marketing application for a different product. PRVs may be sold or transferred, and there is no limit on the number of times a PRV can be transferred.

On October 30, 2023 Biomea Fusion, Inc. ("Biomea" or "the Company") (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, reported third quarter 2023 financial results and business highlights (Press release, Biomea Fusion, OCT 30, 2023, View Source [SID1234636431]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With the disease modifying potential demonstrated by BMF-219, we are excited to begin the expansion portion of COVALENT-111 in type 2 diabetes, and to initiate the evaluation of BMF-219’s impact in type 1 diabetes with our COVALENT-112 study. Both studies are now open for enrollment more than a quarter ahead of schedule. With the potential to enable patients to retain and regenerate their own insulin-producing beta cells, BMF-219 may represent a promising new approach, if ultimately approved. We believe BMF-219 has the potential to halt and reverse disease progression for people with both type 1 and type 2 diabetes, enabling them to improve glycemic control while being off therapy and avoid insulin dependency," said Thomas Butler, CEO and Chairman of Biomea. "In the third quarter, we also announced the first clinical data of BMF-219 in relapsed/refractory AML patients with menin-dependent mutations, which we believe yield encouraging efficacy and safety data. Finally in this quarter, we also initiated the clinical study of our second, Biomea-discovered investigational covalent inhibitor, BMF-500, a novel FLT3 inhibitor. We look forward to reporting on our pipeline progress in both diabetes and oncology in the upcoming quarters."

THIRD QUARTER 2023 CLINICAL AND REGULATORY HIGHLIGHTS

DIABETES

COVALENT-111 (BMF-219 for Type 2 Diabetes)
BMF-219 is an investigational diabetes therapy that in an early clinical trial has shown promising blood glucose control in adults with uncontrolled type 2 diabetes at Week 12, after 4 weeks dosing and 8 weeks off treatment.
During the escalation phase of COVALENT-111, a total of 32 type 2 diabetes patients completed 4-weeks of dosing with BMF-219 to date (10 active patients per arm, with dose levels 100 mg with food, 100 mg, 200 mg and 200 mg with food (n=2)). Compared to baseline, 84% of all patients dosed for four weeks with BMF-219 showed a reduction in HbA1c at Week 4 and 74% at Week 12 (n=32), two months after the final dose of BMF-219. During the 4-week dosing period, BMF-219 was generally well tolerated; there were no dose reductions, dose discontinuations, or severe or serious adverse events. Also, during the off-treatment period, no severe or serious treatment emergent adverse events were noted.
FDA and Health Canada cleared the initiation of the expansion portion of COVALENT-111, which will evaluate BMF-219 administered at 100 mg and 200 mg, with dosing durations up to 12 weeks in approximately 200 type 2 diabetes patients.
Anticipated Upcoming Milestones:
Report topline data for the escalation portion in Q4 2023 to include multiple BMF-219 dosing cohorts (n=10 per cohort: 50 mg, 100 mg, 200 mg, 100 mg BID, 100 mg with food, and 200 mg with food (n=2)).
Start enrollment of expansion portion of COVALENT-111 at two dose levels including 100 mg and 200 mg, with a fourth cohort following the completion of the escalation portion.
COVALENT-112 (BMF-219 for Type 1 Diabetes)
BMF-219 has shown the potential to specifically regenerate and retain insulin-producing beta cells in preclinical studies.
Announced FDA clearance of IND for Phase II study COVALENT-112 of BMF-219 in type 1 diabetes. The study is designed to enroll 150 adults with type 1 diabetes and examine the safety and efficacy of BMF-219 at two oral dose levels, 100 mg and 200 mg, for 12 weeks of treatment followed by a 40 week off-treatment period.
Anticipated Upcoming Milestones:
Dose the first patient in COVALENT-112.
ONCOLOGY

COVALENT-101 (BMF-219 for Oncology)
Reported initial topline data from ongoing Phase I clinical trial (COVALENT-101) which showcased initial responses in relapsed/refractory AML patients with menin-dependent mutations.
New data revealed 2 CRs out of 5 pretreated patients with relapsed/refractory AML patients carrying menin-dependent mutations (MLL1r, NMP1, MLL1-PTD, and NUP98 fusion) treated at Dose Level 4.
BMF-219, the first and only investigational covalent small-molecule menin inhibitor in clinical development, was generally well tolerated with no dose-limiting toxicities observed, and no related QTc prolongation reported.
Continued site activation and patient enrollment to establish optimal dose levels across four liquid tumor cohorts including patients with AML/ALL, DLBCL, MM and CLL.
Anticipated Upcoming Milestones:
Report additional details of the clinical data set of AML/ALL patients dosed in the COVALENT-101 study at an upcoming medical conference.
COVALENT-102 (BMF-219 for KRAS-Mutant Solid Tumors)
BMF-219 is the first investigational menin inhibitor in clinical development for the treatment of solid tumors; as a pan-KRAS inhibitor BMF-219 is under evaluation in subsets of NSCLC, CRC, and PDAC patients.
Continued site activation and patient enrollment to establish optimal dose levels across all three solid tumor indications (NSCLC, CRC and PDAC with an activating KRAS mutation).
COVALENT-103 (BMF-500 for Acute Leukemias)
Dosed first patient with BMF-500, a novel investigational third generation oral covalent inhibitor of FLT3 and the second product candidate discovered and developed by Biomea’s proprietary FUSION System.
FUSIONTM SYSTEM PLATFORM / ONGOING EFFORTS

Continued to advance development candidates derived from Biomea’s proprietary FUSION System platform to discover novel covalently binding small molecules. Both BMF-219 and BMF-500 were discovered via the FUSION System, each within 18 months from target identification to IND candidate selection.
THIRD QUARTER 2023 FINANCIAL RESULTS

Cash, Cash Equivalents, Restricted Cash, and Investments: As of September 30, 2023, the Company had cash, cash equivalents, restricted cash, and investments of $199.5 million, compared to $113.4 million as of December 31, 2022.
Net Income/Loss: Biomea reported a net loss attributable to common stockholders of $28.4 million for the three months ended September 30, 2023, compared to a net loss of $22.9 million for the same period in 2022. Net loss attributable to common stockholders was $82.4 million for the nine months ended September 30, 2023, compared to a net loss of $56.5 million for the same period in 2022.
Research and Development (R&D) Expenses: R&D expenses were $25.3 million for the three months ended September 30, 2023, compared to $18.2 million for the same period in 2022. The increase of $7.1 million was primarily due to an increase clinical development cost and external consulting related to the Company’s product candidates, BMF-219 and BMF-500, as well as increase in personnel-related costs. R&D expenses were $71.7 million for the nine months ended September 30, 2023 compared to $42.2 million for the same period in 2022. The increase of $29.5 million was primarily due to an increase personnel-related costs as well as an increase in clinical development and manufacturing costs related to the Company’s product candidates, BMF-219 and BMF-500.
General and Administrative (G&A) Expenses: G&A expenses were $5.8 million for the three months ended September 30, 2023, compared to $5.2 million for the same period in 2022. G&A expenses were $17.1 million for the nine months ended September 30, 2023 compared to $15.2 million for the same period in 2022. The increase in both periods was primarily due to increased personnel-related expenses, including stock-based compensation, due to an increase in headcount.

On October 30, 2023 Bicycle Therapeutics plc (NASDAQ:BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that management will participate in the following investor conferences in November (Press release, Bicycle Therapeutics, OCT 30, 2023, View Source [SID1234636430]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

TD Cowen 7th Annual Fall Oncology Innovation Summit on Friday, November 3, 2023; fireside chat at 10:00 a.m. ET
Jefferies London Healthcare Conference on Wednesday, November 15, 2023; fireside chat at 11:00 a.m. ET

Live webcasts of the fireside chats will be accessible in the Investors section of Bicycle’s website at www.bicycletherapeutics.com. Archived replays of the webcasts will be available following the fireside chat dates.