On December 5, 2023 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology," Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, reported interim results from an ongoing Phase 1b/2 clinical study of palazestrant (OP-1250) in combination with CDK4/6 inhibitor ribociclib, a Poster Spotlight Session on interim Phase 2 clinical data of palazestrant in combination with palbociclib, and a trials-in-progress poster for the OPERA-01 monotherapy Phase 3 pivotal trial at the San Antonio Breast Cancer Symposium (SABCS) at the Henry B. Gonzalez Convention Center in San Antonio, Texas (Press release, Olema Oncology, DEC 5, 2023, View Source [SID1234638165]). This disclosure was originally planned for December 7, 2023. However, on December 5, 2023, the 2023 San Antonio Breast Cancer Symposium (SABCS) published the posters ahead of schedule. These full data are scheduled to be presented on December 7, 2023, and copy of the posters are available now on Olema’s website under the Science section.

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"We believe the results we are presenting at SABCS demonstrate that palazestrant has key characteristics that make it a potential best-in-class endocrine therapy for ER+/HER2- breast cancer: complete antagonism of the estrogen receptor, favorable tolerability and tumor response, and attractive combinability with CDK4/6 inhibitors," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "OPERA-01, our Phase 3 monotherapy pivotal trial of palazestrant, has initiated, with multiple trial sites now activated and patient dosing started. The data we are gathering in our Phase 2 combination studies with CDK4/6 inhibitors, ribociclib and palbociclib, support the potential initiation of a pivotal first-line combination trial as early as the end of 2024, bringing us closer to achieving our goal of transforming the standard of care for women’s cancers."

Palazestrant Phase 1b/2 Study in Combination with Ribociclib: A poster titled "A Phase 1b/2 study of palazestrant (OP-1250) in combination with ribociclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced and/or metastatic breast cancer" will be presented at SABCS. A more recent data cut, as of November 1, 2023, highlights the following:

•Across 19 patients who had completed at least one cycle of treatment as of the data cutoff date, the combination of up to 120 mg of palazestrant with 600 mg of ribociclib daily was well tolerated, with no safety signals or enhancement of toxicity and an overall safety profile remains consistent with the expected safety profile of ribociclib plus an endocrine therapy.
•Palazestrant did not affect ribociclib drug exposure in patients, and ribociclib had no clinically meaningful effect on palazestrant drug exposure.
•There were no dose-limiting toxicities, the maximum tolerated dose was not reached, and the majority of treatment-emergent adverse events were grade 1 or 2, with no grade 4 events observed. Neutropenia was reversible in all patients, and the timing was generally consistent with ribociclib-related neutropenia.
•Findings from this study support the continued use of palazestrant at the recommended Phase 2 dose of 120 mg in combination with 600mg of ribociclib, and enrollment in the dose-expansion portion of the study is ongoing.

Palazestrant Phase 1b/2 Study in Combination with Palbociclib: A poster titled "A Phase 1b/2 study of palazestrant (OP-1250), an oral complete estrogen receptor antagonist (CERAN) and selective ER degrader (SERD), with palbociclib in ER-positive, HER2-negative, advanced or metastatic breast cancer patients", will be presented in a Poster Spotlight Session by Prof. Arlene Chan, FRACP, MMed, Breast Cancer Research Centre-WA, Curtin University, Breast Clinical Trials Unit, Hollywood Private Hospital, Nedlands, Australia. The presentation will highlight that:

•
Across 46 patients as of the cutoff date of September 15, 2023, the combination of palazestrant (120 mg) with palbociclib (125 mg) daily was well tolerated, with an overall safety profile consistent with the expected safety profile of palbociclib plus an endocrine therapy.
•
There was no observed drug-drug interaction between palazestrant and palbociclib, and there was no induced metabolism or increase in exposure of either palbociclib or palazestrant when administered in combination. Most treatment-emergent adverse events were grade 1 or 2. Neutropenia incidence was similar to the PALOMA-3 study; it was reversible in all patients and the timing was generally consistent with the palbociclib-related neutropenia.
•
Tumor responses and prolonged disease stabilization were observed in this patient group, including in those previously exposed to CDK4/6 inhibitors, in both ESR1 mutant and ESR1 wild-type tumors. Partial responses were observed in seven patients, with two confirmed partial responses and five unconfirmed partial responses. The clinical benefit rate was 46% in all patients and 60% in patients with an ESR1 mutation at baseline. In patients naïve to prior CDK4/6 inhibitor treatment, the CBR was 71%. 53% of patients had any reduction in target lesion size.
•
Twenty-two (48%) patients remain on treatment, and efficacy data are still maturing. Findings from this study are consistent with previously reported data and support the ongoing clinical development of palazestrant in combination with CDK4/6 inhibitors for the treatment of ER+/HER2− metastatic breast cancer.

OPERA-01 Phase 3 Monotherapy Trial: Olema will present a poster titled "OPERA-01: A randomized, open-label, phase 3, study of palazestrant (OP-1250) vs standard-of-care treatment for ER+, HER2- advanced or metastatic breast cancer after endocrine and CDK4/6 inhibitor therapy", that detailed the ongoing clinical trial design, inclusion/exclusion criteria, and trial endpoints. Please find more details at www.opera-01.com or at clinicaltrials.gov (NCT06016738).

Company Investor Webcast and Conference Call

Olema will host a webcast and conference call for analysts and investors to review data presented at SABCS 2023 as well as other ongoing studies tomorrow, Wednesday, December 6, 2023, at 8:00 a.m. ET (7:00 a.m. CT). Please register for the webcast by visiting the Investors & Media section of Olema’s website at olema.com.

On December 05, 2023 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company creating and developing engineered IgM antibodies, reported that it will focus its resources in two strategic areas: (i) treating colorectal cancer using IgM death receptor 5 (DR5) agonist antibodies, and (ii) treating autoimmune diseases using IgM T cell engager antibodies (Press release, IGM Biosciences, DEC 5, 2023, View Source [SID1234638164]). As an expansion of its autoimmune efforts, the Company also announced today that it plans to file an Investigational New Drug (IND) application to begin the clinical development of IGM-2644, its CD38 x CD3 T cell engager antibody, for the treatment of autoimmune diseases. As part of its strategic refocus, the Company is halting all hematologic oncology clinical development as well as the clinical development of its targeted cytokine product candidate. The Company will continue to focus on the development of oncology and immunology and inflammation product candidates under its collaboration with Sanofi. In conjunction with this strategic refocusing, the Company will be reducing its workforce by approximately 22 percent. As a result of these actions, IGM expects to extend its cash runway into the second quarter of 2026.

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"IGM continues to have a tremendous opportunity to transform a variety of disease areas using an entirely new class of antibody medicines," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "Although we are very encouraged by the clinical and preclinical data that we have generated for the programs we are halting, given the difficult conditions in the capital markets for our industry, we have decided to focus our capital resources on those opportunities that we believe have the most potential to produce significant near-term value. We are very sorry that some of our dedicated and talented employees will be leaving IGM as part of this strategic refocusing, and we wish to extend our sincere thanks and assistance to them in this difficult transition."

Pipeline Update:

Aplitabart (DR5 agonist)

Clinical development of aplitabart in colorectal cancer prioritized.
Enrollment continues in randomized colorectal cancer clinical trial. The Company continues to enroll patients in a randomized clinical trial of aplitabart, a death receptor 5 agonist, plus FOLFIRI and bevacizumab in second-line metastatic colorectal cancer, with a goal of enrolling approximately 110 patients by the end of the first quarter of 2024. In addition to clinical trial sites in the United States, this trial includes multiple clinical trial sites in Asia and Europe.
Treatment at 10 mg/kg ongoing in the single arm colorectal cancer clinical trial continues. The Company also continues to treat later line colorectal cancer patients in its single arm combination clinical trial of 10 mg/kg of aplitabart and FOLFIRI. The Company expects to complete enrollment of patients in this 10 mg/kg single arm combination study in the first half of 2024.
Imvotamab (CD20 x CD3)

Clinical development of imvotamab in autoimmune diseases prioritized. The Company is prioritizing the clinical development of imvotamab, an IgM-based CD20 x CD3 bispecific T cell engaging antibody in autoimmune diseases. The Company currently has two Phase 1b clinical trials underway, one in severe systemic lupus erythematosus (SLE) and one in severe rheumatoid arthritis (RA). These clinical trials are being expanded to include multiple U.S. and international clinical trial sites. The Company also recently received clearance from the FDA of its IND application for the use of imvotamab in treating idiopathic inflammatory myopathies (myositis), and preparations are underway to move this clinical trial forward.
IGM-2644 (CD38 x CD3)

Clinical development of IGM-2644 in autoimmune diseases prioritized. The Company is prioritizing the clinical development of IGM-2644, a CD38 x CD3 T cell engager antibody, in the treatment of autoimmune diseases, and it plans to file an IND for these purposes in 2024.
As a part of this strategic refocusing, the Company will halt the following clinical development activities:

Aplitabart in acute myeloid leukemia and in combination with birinapant
IGM-2644 (CD38 x CD3) in multiple myeloma
IGM-2537 (CD123 x CD3)
IGM-7354 (IL-15 x PD-L1)

On December 5, 2023 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition"), a multi-national epigenetics company, reported the company has closed on an aggregate of Euro 5.0 million (approximately $5.5 million) in financing from Wallonie Entreprendre S.A. ("WE") in Belgium (Press release, VolitionRX, DEC 5, 2023, View Source [SID1234638163]).

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Volition will use the proceeds from the financing for ongoing development of its Nu.Q product portfolio, including taking forward its clinical and regulatory program for Nu.Q NETs, which it believes will aid the early diagnosis of diseases such as sepsis.

Volition is currently working with leading clinicians and researchers at centers of excellence worldwide to help facilitate the effective introduction of Nu.Q NETs into clinical practice.

The Euro 5.0 million financing from WE consists of a Euro 2.5 million unsecured loan to Volition’s subsidiary, Belgian Volition SRL, and a Euro 2.5 million purchase of 3,205,431 shares of Volition’s restricted common stock at a purchase price of $0.8337 per share in a private placement transaction. The unsecured loan bears interest at a rate of approximately 8% per year and has a stated maturity date of December 31, 2028. Subject to certain conditions, the loan can be drawn down in three tranches at Belgian Volition’s election on or prior to June 30, 2025, with Euro 1.5 million available immediately, Euro 0.5 million available from June 1, 2024 and the final Euro 0.5 million available from March 1, 2025.

Gaetan Michel, Chief Operating Officer of Volition, said: "We are enormously grateful to WE for this latest financing, and for the ongoing financial assistance we have received from agencies within Wallonia to date."

Volition is developing simple, easy-to-use, cost-effective blood tests to help diagnose and monitor a range of life-altering diseases in both humans and animals. For more information about Volition’s Nu.Q technology go to: www.volition.com

The shares of restricted common stock were issued by Volition to WE in a private placement in reliance on an exemption from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"), and the rules and regulations promulgated thereunder. The shares of common stock will not be registered under the Securities Act or any state securities laws and unless so registered may not be offered or sold in the United States except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities laws. This announcement is neither an offer to sell nor a solicitation of an offer to buy any securities.

On December 5, 2023 Thermo Fisher Scientific reported the company issued $1,000,000,000 aggregate principal amount of 5.000% Senior Notes due 2026 (the "2026 Notes"), $1,000,000,000 aggregate principal amount of 5.000% Senior Notes due 2029 (the "2029 Notes") and $500,000,000 aggregate principal amount of 5.200% Senior Notes due 2034 (the "2034 Notes" and, collectively with the 2026 Notes and the 2029 Notes, the "Notes") in a public offering (the "Offering") pursuant to a registration statement on Form S-3 (File No. 333-263034) and a preliminary prospectus supplement and prospectus supplement related to the offering of the Notes, each as previously filed with the Securities and Exchange Commission (Press release, Thermo Fisher Scientific, DEC 5, 2023, View Source [SID1234638162]). The Notes were issued under an indenture, dated as of November 20, 2009 (the "Base Indenture"), and the Twenty-Eighth Supplemental Indenture, dated as of December 5, 2023 (the "Supplemental Indenture" and, together with the Base Indenture, the "Indenture"), between the Company, as issuer, and The Bank of New York Mellon Trust Company, N.A., as trustee.

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The 2026 Notes will mature on December 5, 2026, the 2029 Notes will mature on January 31, 2029 and the 2034 Notes will mature on January 31, 2034. Interest on the 2026 Notes will be paid semi-annually in arrears on June 5 and December 5 of each year, commencing on June 5, 2024. Interest on the 2029 Notes and the 2034 Notes will be paid semi-annually in arrears on January 31 and July 31 of each year, commencing on July 31, 2024.

Prior to November 5, 2026, in the case of the 2026 Notes, December 31, 2028, in the case of the 2029 Notes, and October 31, 2033, in the case of the 2034 Notes (each, a "Par Call Date"), the Company may redeem each series of the Notes, in whole at any time or in part from time to time, at a redemption price equal to the greater of (1) 100% of the principal amount of the Notes of such series to be redeemed and (2) the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes of such series being redeemed (not including any portion of the payments of interest accrued but unpaid as of the date of redemption and assuming that such Notes to be redeemed matured on their applicable Par Call Date), discounted to the date of redemption on a semi-annual basis (assuming a 360-day year of twelve 30-day months), at the Treasury Rate (as defined in the Indenture) plus 10 basis points, in the case of the 2026 Notes, 15 basis points, in the case of the 2029 Notes, and 15 basis points, in the case of the 2034 Notes, plus, in each case, accrued and unpaid interest on the Notes of such series being redeemed, if any, to, but excluding, the date of redemption.

In addition, on and after the applicable Par Call Date, the Company may redeem some or all of each series of the Notes at a redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding the date of redemption.

Upon the occurrence of a change of control (as defined in the Indenture) of the Company and a contemporaneous downgrade of the Notes below an investment grade rating by at least two of Moody’s Investors Service, Inc., S&P Global Ratings, a division of S&P Global, Inc., and Fitch Ratings, Limited, the Company will, in certain circumstances, be required to make an offer to purchase the Notes at a price equal to 101% of the principal amount of the Notes, plus any accrued and unpaid interest to, but excluding, the date of repurchase.

The Notes are general unsecured obligations of the Company. The Notes rank equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of the Company and rank senior in right of payment to any existing and future indebtedness of the Company that is subordinated to the Notes. The Notes are also effectively subordinated to any existing and future secured indebtedness of the Company to the extent of the assets securing such indebtedness, and are structurally subordinated to all existing and any future indebtedness and any other liabilities or commitments of its subsidiaries.

The Indenture contains limited affirmative and negative covenants. The negative covenants restrict the ability of the Company and its subsidiaries to incur debt secured by liens on Principal Properties (as defined in the Indenture) or on shares of capital stock of any of our direct or indirect subsidiaries that owns a Principal Property and engage in sale and lease-back transactions with respect to any Principal Property. The Indenture also limits the ability of the Company to merge or consolidate or sell all or substantially all of its assets.

Upon the occurrence of an event of default under the Indenture, which includes payment defaults, defaults in the performance of affirmative and negative covenants, bankruptcy and insolvency related defaults and failure to pay certain indebtedness, the obligations of the Company under the Notes may be accelerated, in which case the entire principal amount of the Notes would be immediately due and payable.

Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Company, has issued an opinion to the Company, dated December 5, 2023, regarding the Notes. A copy of this opinion is filed as Exhibit 5.1 hereto.

The foregoing description is qualified in its entirety by reference to the full text of the Base Indenture and the Supplemental Indenture, which are filed with this report as Exhibits 4.1 and 4.2 hereto, respectively. Each of the foregoing documents is incorporated herein by reference.

Item 8.01. Other Events.

The sale of the Notes was made pursuant to the terms of an Underwriting Agreement, which the Company entered into on November 28, 2023 (the "Underwriting Agreement"), with BofA Securities, Inc., Morgan Stanley & Co. LLC, U.S. Bancorp Investments, Inc. and Wells Fargo Securities, LLC, as representatives of the several underwriters named in Schedule A to the Underwriting Agreement.

The Company expects that the net proceeds from the sale of the Notes will be approximately $2.48 billion, after deducting underwriting discounts and estimated offering expenses. The Company intends to use the net proceeds of the Offering for general corporate purposes, which may include the acquisition of companies or businesses, repayment and refinancing of debt, working capital and capital expenditures or the repurchase of its outstanding equity securities or the Company may temporarily invest the net proceeds in short-term, liquid investments until they are used for their ultimate purpose.

The foregoing description is qualified in its entirety by reference to the full text of the Underwriting Agreement, which is filed with this report as Exhibit 1.1 hereto and is incorporated herein by reference.

On December 5, 2023 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported the pricing of an underwritten public offering of 9,482,758 shares of its common stock at a public offering price of $29.00 per share (Press release, SpringWorks Therapeutics, DEC 5, 2023, View Source [SID1234638161]). All of the shares in the offering are being sold by SpringWorks. The gross proceeds from the offering, before deducting underwriting discounts and commissions and estimated offering expenses, are expected to be approximately $275.0 million. The offering is expected to close on or about December 7, 2023, subject to the satisfaction of customary closing conditions. In addition, SpringWorks has granted the underwriters a 30-day option to purchase up to an additional 1,422,413 shares of its common stock at the public offering price, less underwriting discounts and commissions.

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Goldman Sachs & Co. LLC, J.P. Morgan Securities LLC, Cowen and Company, LLC and Guggenheim Securities, LLC are acting as joint book-running managers for the offering.

An automatic shelf registration statement on Form S-3ASR (including a prospectus) relating to these securities has been filed with the Securities and Exchange Commission (SEC) and has become effective.

The offering is being made only by means of a prospectus and prospectus supplement that form part of the automatic shelf registration statement. A preliminary prospectus supplement describing the terms of the offering has been filed with the SEC and forms a part of the effective registration statement. A copy of the final prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and may be obtained, when available, from: Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, or by telephone at (866) 471-2526 or by email at [email protected]; J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1115 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Cowen and Company, LLC, 599 Lexington Avenue, New York, NY 10022, by email at [email protected] or by telephone at (833) 297-2926; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, or by telephone at (212) 518-9544, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any 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.