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Exelixis Highlights Positive Results for CABOMETYX® (cabozantinib) in Patients with Metastatic Papillary Renal Cell Carcinoma in SWOG S1500/PAPMET Study at ASCO GU

On February 13, 2021 Exelixis, Inc. (NASDAQ: EXEL) reported positive phase 2 results for CABOMETYX (cabozantinib) compared with sunitinib, the current preferred therapy according to U.S. cancer treatment guidelines,1 in patients with metastatic papillary renal cell carcinoma (PRCC), a form of kidney cancer (Press release, Exelixis, FEB 13, 2021, View Source [SID1234575057]). The data from the S1500 trial (also called "PAPMET"), which was designed and managed by SWOG Cancer Research Network, will be presented on Saturday, February 13th during the Oral Abstract Session: Renal Cell Cancer at 10:00 – 11:15 a.m. PT at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Genitourinary Cancers Symposium (ASCO GU), which is being held virtually, February 11-13, 2021. The findings will be simultaneously published in The Lancet.

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"This is the first randomized trial specific to metastatic papillary renal cell carcinoma to show a clinically and statistically significant benefit with a targeted therapy, CABOMETYX, over an existing standard of care," said Dr. Sumanta Pal, Clinical Professor and Co-Director of the Kidney Cancer Program, City of Hope, and SWOG’s principal investigator for the study. "The progression-free survival benefit seen in this trial is a meaningful improvement for patients with this form of kidney cancer. Based on these findings, there is strong evidence for the use of CABOMETYX in this setting."

"The PAPMET trial was sponsored by the National Cancer Institute’s drug development program in the Cancer Therapy Evaluation Program, which facilitates collaborations between pharmaceutical companies as well as collaborations between companies and academic investigators. In the case of PAPMET, the National Cancer Institute brought Exelixis, AstraZeneca and Pfizer together with oncologists from SWOG to organize this trial to define which of the tested therapies is most effective for patients with papillary renal cell carcinoma," said Dr. John Wright, Associate Branch Chief, Investigational Drug Branch, CTEP, NCI.

In the new findings, CABOMETYX demonstrated significant improvement in progression-free survival (PFS), the trial’s primary endpoint, and objective response rate (ORR) compared with sunitinib. Median PFS was 9.0 months (95% CI: 6-12) with CABOMETYX (n=44) versus 5.6 months (95% CI: 3-7) with sunitinib (n=46) (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.37 to 0.97; p=0.019). ORR was 23% for CABOMETYX versus 4% for sunitinib (p=0.010). Median overall survival was 20.0 months for cabozantinib and 16.4 months for sunitinib (HR 0.84; 95% CI: 0.47 to 1.51; p=0.28), which did not reach statistical significance. Enrollment into additional arms of the study examining the use of crizotinib or savolitinib was halted early based on predefined interim futility analyses comparing these agents with the sunitinib arm.

"We’re excited to build on the demonstrated history of CABOMETYX’s clinically meaningful and statistically significant benefits for patients with renal cell carcinoma with these data that support its efficacy in patients with papillary renal cell carcinoma, who are often not the focus of major clinical trials for kidney cancer," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "The ability of CABOMETYX to inhibit MET, which is frequently altered in this tumor type, encouraged additional research into its potential benefits. It’s gratifying to see these positive results of the PAPMET trial, which may help physicians choose an appropriate therapy for their patients with advanced papillary renal cell carcinoma."

The discontinuation rate of study medications due to treatment-related adverse events was 24% for sunitinib and 23% for CABOMETYX. The most common grade 3 or 4 adverse events with CABOMETYX were hypertension (32%), hand-foot syndrome (20%) and fatigue (13%). The most common grade 3 or 4 adverse events with sunitinib were hypertension (17%), anemia (13%) and decrease in white blood cell count (11%). One death, secondary to a thromboembolic event, within 30 days of the last dose of study medication was reported for a patient receiving CABOMETYX.

More information about this trial is available at ClinicalTrials.gov.

About the SWOG S1500 Clinical Trial

SWOG S1500 (NCT02761057), also called PAPMET, was a randomized phase 2 trial comparing cabozantinib, crizotinib and savolitinib to sunitinib, a VEGF-directed multikinase inhibitor and current standard of care for patients with advanced or metastatic PRCC. The study was supported by the National Cancer Institute (NCI), part of the National Institutes of Health, designed and led by the SWOG Cancer Research Network under the leadership of Dr. Pal, and conducted through the NCI National Clinical Trials Network. The goal of the trial was to determine whether MET-directed therapy improves clinical outcomes relative to conventional VEGF-directed agents. Exelixis provided the cabozantinib for the trial under a Cooperative Research and Development Agreement with the NCI.

Patients with pathologically verified PRCC (type I, II, or not otherwise specified) were randomized 1:1:1:1 to the control arm of sunitinib or one of three investigational arms: CABOMETYX, crizotinib and savolitinib. CABOMETYX was orally administered at 60 mg daily, with dose reductions to 40 mg and 20 mg permitted. Enrolled patients could have received up to one prior therapy. Prior therapy was received by 10 patients (7%), and the most common prior therapy was the combination of nivolumab with ipilimumab (4 patients). The primary endpoint was PFS, defined as the time from randomization to the time of radiographic or clinical progression, symptomatic deterioration or death from any cause, whichever occurred first. Secondary endpoints included objective response rate and overall survival, defined as the time from randomization to death from any cause, and safety evaluation.

About Papillary Renal Cell Carcinoma

PRCC accounts for about 15% of all renal cell carcinomas.2,3 Genomic and molecular characterization of PRCC has implicated MET signaling as a key driver of this cancer.2,4 Targeting VEGFR and other tyrosine kinases, including MET and AXL, has led to improved outcomes in RCC as compared with sunitinib, and further supported the investigation of MET targeting tyrosine kinase inhibitors in PRCC.

The American Cancer Society’s 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.5 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.4 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021.6

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

bridgebio pharma, inc. announces pricing of secondary offering of common stock

On February 12, 2021 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (the "Company," "we" or "BridgeBio") reported the pricing of a secondary public offering of 3,000,000 shares of its common stock at a price per share of $62.50 by selling stockholder KKR Genetic Disorder L.P (Press release, BridgeBio, FEB 12, 2021, View Source [SID1234576235]). The selling stockholder has also granted the underwriters a 30-day option to purchase up to 450,000 additional shares of common stock on the same terms and conditions. All shares are being sold by KKR Genetic Disorder L.P. The Company is not selling any shares and will not receive any of the proceeds of the offering. The offering is expected to close on February 17, 2021, subject to customary closing conditions.

Goldman Sachs & Co. LLC is acting as the sole book-running manager, and KKR Capital Markets LLC and Raymond James & Associates, Inc. are acting as co-managers for the offering.

The securities described above are being offered pursuant to an automatic shelf registration statement on Form S-3 (File No. 333-240147) that was previously filed by the Company with the Securities and Exchange Commission (the "SEC") and automatically became effective upon filing on July 28, 2020.

A preliminary prospectus supplement and accompanying prospectus relating to the offering are filed with the SEC and are available on the SEC’s website at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus and, when available, copies of the final prospectus supplement and accompanying prospectus can be obtained by contacting Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at 1 866 471 2526, or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities described above, 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.

Entry Into a Material Definitive Agreement

On February 12, 2021, Nektar Therapeutics (the "Company") reprted that entered into a co-development agreement (the "Agreement") with SFJ Pharmaceuticals XII, L.P., an SFJ Pharmaceuticals Group company ("SFJ"), pursuant to which SFJ will pay up to $150 million in committed funding to support a Phase 2/3 study of bempegaldesleukin ("BEMPEG") in combination with KEYTRUDA (pembrolizumab) for first-line treatment of patients with metastatic or unresectable recurrent squamous cell carcinoma of the head and neck (the "HNC Clinical Trial") whose tumors express PD-L1 (the "HNC Indication") (Filing, 8-K, Nektar Therapeutics, FEB 12, 2021, View Source [SID1234575180]). SFJ’s $150 million funding commitment is not contingent on any other BEMPEG development program outcomes.

During the term of the Agreement, SFJ will have primary responsibility for the clinical trial management of the HNC Clinical Trial and serves as a contract research organization as defined by 21 C.F.R. 312.52. The Company will be the sponsor of the HNC Clinical Trial and will also have sole responsibility for regulatory interactions and approval activities for BEMPEG in all indications. The Company and Bristol-Myers Squibb, pursuant to their Strategic Collaboration Agreement dated February 13, 2018, remain solely responsible for the Phase 3 clinical trial of BEMPEG in combination with OPDIVO (nivolumab) for the treatment of previously untreated unresectable or metastatic melanoma (the "Melanoma Indication" and together with the HNC Indication, the "Indications") (the "Melanoma Clinical Trial").

The Company and SFJ have agreed to use commercially reasonable efforts to conduct and complete the HNC Clinical Trial activities for which each is responsible in accordance with the timeline agreed to by the Parties. The Company and SFJ will form a joint steering committee to oversee and manage the collaboration. Further, the Company has agreed that if the HNC Clinical Trial meets specified trial success criteria, it will use commercially reasonable efforts to file a biologics license application (a "BLA") with the United States Food and Drug Administration (the "FDA"), and that if the Melanoma Clinical Trial meets specified trial success criteria, it will use commercially reasonable efforts to file a BLA.

The Company will pay SFJ, subject to the buy-out provision described below, a series of success-based annual payments following FDA approval of BEMPEG for the Melanoma Indication, the HNC Indication, or both, and FDA approval of one additional BEMPEG indication. Payments will not start until the completion of the HNC Clinical Trial activities as defined below. The total success-based annual payments for the first indication approved by FDA, whether for the Melanoma Indication or the HNC Indication, is an aggregate of $450 million ("First Indication Amount") paid on an annual basis over a period of five years. The total success-based payments for the second indication approved by FDA, whether for the Melanoma Indication or the HNC Indication, is an aggregate of $150 million ("Second Indication Amount") paid on an annual basis over a period of seven years. If FDA approval of the Melanoma Indication occurs before FDA approval of the HNC Indication, the first annual success payment would be due within 30 days of the completion of the HNC Clinical Trial activities defined as the earlier of (i) the date on which the database lock for the primary endpoint of median overall survival to be used for a full approval submission to FDA for HNC Indication occurs, or (ii) the 18-month anniversary of the last patient enrolled into the HNC Clinical Trial (the earliest date being the "First Payment Date"). The first annual success payment for the First Indication Amount is $30 million payable on or before the First Payment Date, after which all additional annual payments for the First Indication Amount will be paid according to a 5-year annual payment schedule. The annual success payments for the Second Indication Amount will be paid according to a 7-year annual payment schedule. Finally, following FDA approval of a BLA for BEMPEG for any indication other than the Melanoma Indication or the HNC Indication, the Company shall make a single payment to SFJ of $37.5 million (the "Additional Indication Payment Amount" and collectively with the First Indication Amount and Second Indication Amount, the "Success Payments"). Other than the opportunity to receive Success Payments as outlined above, SFJ has no right to reimbursement of costs incurred by SFJ for the HNC Clinical Trial in the event that the Melanoma Clinical Trial and/or the HNC Clinical Trial do not meet their primary endpoints.

The Company has the right, at its option, to make a one-time cash payment to SFJ to buy out all of the First Indication Amount at a prespecified annual discount rate. This buy-out option is exercisable by the Company within 180 days of the First Payment Date. The Company also has the right, at its option, to make a one-time cash payment to SFJ to buy out all of the Second Indication Amount, at a prespecified annual discount rate. This buy-out option is exercisable by the Company within 180 days of the approval date for the second indication approved by FDA. Within 45 days following a change of control of the Company, the Company shall make a one-time cash payment to SFJ equal to 150% of development costs paid or incurred by SFJ prior to such change of control, to be credited toward future Success Payments in the order in which they become due.

The Company has agreed to certain affirmative and negative covenants, including restrictions on the Company’s ability to incur liens on its intellectual property that is necessary or useful for the development, manufacture, use, sale or import of BEMPEG (the "BEMPEG IP"), or assign or convey any right to receive income with respect to the BEMPEG IP (other than royalty and other license fee obligations to licensors thereof in accordance with the applicable license agreement), except for the issuance of senior secured debt secured by all or substantially all of the Company’s assets, including the BEMPEG IP.

The Agreement expires upon the payment of all Success Payments to SFJ, unless earlier terminated. The Agreement may be terminated by either party (a) for material breach by the other party, following a specified cure period, (b) upon the other party’s bankruptcy, (c) if the independent data monitoring committee for the HNC Clinical Trial recommends termination of the trial for safety or health reasons or for futility and the Company reasonably believes there is a basis for such termination, (d) if the parties mutually agree a material health or safety concern with respect to the subjects of the HNC Clinical Trial exists or (e) upon a breach by the other party involving improper payments or a violation of anti-corruption policies. The Agreement may be terminated by SFJ (a) for failure by the Company to make a Success Payment when due, following the lapse of a specified cure period, (b) in the event that any HNC Clinical Trial does not meet its overall survival primary endpoint, (c) if the Company is prevented from further developing or commercializing BEMPEG for any of the Indications and the future value of BEMPEG would likely be materially adversely affected due to certain third party patents that would be infringed by the manufacture, use, sale, offer for sale or import of BEMPEG or (d) in the event of certain disagreements among the JSC. In certain instances, upon the termination of the agreement, the Company will be obligated to pay SFJ a multiple of the amounts paid by SFJ for development cost funding under the agreement, including specifically: (i) 300% in the event the agreement is terminated due to a safety concern of which the Company had knowledge prior to the date of the Agreement and did not disclose to SFJ; (ii) 150% upon a breach by the Company involving improper payments or a violation of anti-corruption policies that impact the likelihood of obtaining regulatory approval; (iii) 100% upon a breach by SFJ involving improper payments or a violation of anti-corruption policies that impact the likelihood of obtaining regulatory approval, less the amount of all documented out-of-pocket expenses incurred by or on behalf of the Company as a result or arising out of such violation by SFJ; (v) 100% in the event of a termination due to third party patents; (iv) 100% in the event of a termination due to the Company’s bankruptcy, subject to adjustments; and (v) 100% plus an amount reflecting interest on the amount paid by SFJ at an annual rate of 25% in the event of termination due to certain disagreements among the JSC.

Caladrius Biosciences, Inc. Announces $65 Million Registered Direct Offerings Priced At-The-Market under Nasdaq Rules

On February 12, 2021 Caladrius Biosciences, Inc. (Nasdaq: CLBS) ("Caladrius" or the "Company"), a clinical-stage biopharmaceutical company dedicated to the development of cellular therapies designed to reverse disease, reported that it has entered into securities purchase agreements with several institutional investors to purchase an aggregate of 24,906,134 shares of its common stock and warrants to purchase up to an aggregate of 12,453,067 shares of common stock at a purchase price of $2.45 per share of common stock and associated warrant in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Caladrius Biosciences, FEB 12, 2021, View Source [SID1234575130]). The warrants have an exercise price of $2.90 per share, will be immediately exercisable, and will expire five years from the issuance date. The registered direct offering is expected to close on or about February 17, 2021, subject to the satisfaction of customary closing conditions.

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering to the institutional investors.

In addition, the Company also announced that it entered into a securities purchase agreement with certain accredited investors to purchase an aggregate of 1,632,652 shares of its common stock and warrants to purchase up to an aggregate of 816,326 shares of common stock in a non-brokered registered direct offering on the same terms as above. Such registered direct offering is also expected to close on or about February 17, 2021, subject to the satisfaction of customary closing conditions.
The gross proceeds from the registered direct offerings are expected to be approximately $65 million before deducting placement agent fees and other offering expenses. The Company currently intends to use the net proceeds from the offering for working capital and general corporate purposes, including the advancement of its CD34+ technology-based clinical programs.

The securities described above are being offered pursuant to a "shelf" registration statement (File No. 333-226319) filed with the Securities and Exchange Commission (SEC) and declared effective on August 2, 2018. Such securities may be offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A prospectus supplement and the accompanying prospectus relating to each of the offerings of the securities will be filed with the SEC. Electronic copies of the prospectus supplement and the accompanying prospectus relating to the offering of the securities to the institutional investors may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by e-mail: [email protected] or by telephone: (646) 975-6996.
This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor there any sales of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction.

FDA APPROVES G1 THERAPEUTICS’ COSELA™ (TRILACICLIB): THE FIRST AND ONLY MYELOPROTECTION THERAPY TO DECREASE THE INCIDENCE OF CHEMOTHERAPY-INDUCED MYELOSUPPRESSION

On February 12, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that the U.S. Food and Drug Administration (FDA) has approved COSELA (trilaciclib) for injection to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC) (Press release, G1 Therapeutics, FEB 12, 2021, View Source [SID1234575071]). It is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to treatment with chemotherapy. COSELA is expected to be commercially available through G1’s specialty distributor partner network in early March.

"The approval of trilaciclib (COSELA) is an important advance in the treatment of patients with extensive-stage small cell lung cancer receiving chemotherapy," said Dr. Jeffrey Crawford, Geller Professor for Research in Cancer in the Department of Medicine and Duke Cancer Institute. "The most serious and life-threatening side effect of chemotherapy is myelosuppression, or damage to the bone marrow, resulting in reduced white blood cells, red blood cells and platelets. Chemotherapy-induced myelosuppression may lead to increased risks of infection, severe anemia, and/or bleeding. These complications impact patients’ quality of life and may also result in chemotherapy dose reductions and delays. To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed. By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy. In clinical trials, the addition of trilaciclib to extensive-stage small cell lung cancer chemotherapy treatment regimens reduced myelosuppression and improved clinical outcomes. The good news is that these benefits of trilaciclib will now be available for our patients in clinical practice."

Chemotherapy is an effective and important weapon against cancer. However, chemotherapy does not differentiate between healthy cells and cancer cells. It kills both, including important hematopoietic stem and progenitor cells (HSPCs) in the bone marrow that produce white blood cells (immune cells that help fight infection), red blood cells (cells that carry oxygen from the lungs to the tissues), and platelets (cells that prevent bleeding from cancer, surgeries, chronic diseases, and injuries). This chemotherapy-induced bone marrow damage, known as myelosuppression, can lead to increased risk of infection, anemia, thrombocytopenia, and other complications. Myeloprotection is a novel approach of protecting HSPCs in the bone marrow from chemotherapy-induced damage. This approach can help reduce some chemotherapy-related toxicity, making chemotherapy safer and more tolerable, while also reducing the need for reactive rescue interventions.

"Chemotherapy is the most effective and widely used approach to treating people diagnosed with extensive-stage small cell lung cancer; however, standard of care chemotherapy regimens are highly myelosuppressive and can lead to costly hospitalizations and rescue interventions," said Jack Bailey, Chief Executive Officer at G1 Therapeutics. "COSELA will help change the chemotherapy experience for people who are battling ES-SCLC. G1 is proud to deliver COSELA to patients and their families as the first and only therapy to help protect against chemotherapy-induced myelosuppression."

COSELA is administered intravenously as a 30-minute infusion within four hours prior to the start of chemotherapy and is the first FDA-approved therapy that helps provide proactive, multilineage protection from chemotherapy-induced myelosuppression. The approval of COSELA is based on data from three randomized, placebo-controlled trials that showed patients receiving COSELA prior to the start of chemotherapy had clinically meaningful and statistically significant reduction in the duration and severity of neutropenia. Data also showed a positive impact on red blood cell transfusions and other myeloprotective measures. The trials evaluated COSELA in combination with carboplatin/etoposide (+/- the immunotherapy atezolizumab) and topotecan chemotherapy regimens. Approximately 90% of all patients with ES-SCLC will receive at least one of these regimens during the course of their treatment.

The majority of adverse reactions reported with COSELA were mild to moderate in severity. The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia. Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis. Grade 3/4 hematological adverse reactions occurring in patients treated with COSELA and placebo included neutropenia (32% and 69%), febrile neutropenia (3% and 9%), anemia (16% and 34%), thrombocytopenia (18% and 33%), and leukopenia (4% and 17%), respectively.

"Quite often, people diagnosed with extensive-stage small cell lung cancer rely on chemotherapy to not only extend their lives, but also to acutely alleviate their symptoms," said Bonnie J. Addario, lung cancer survivor, co-founder and board chair of the Go2 Foundation for Lung Cancer. "Unfortunately, the vast majority will experience chemotherapy-induced side effects, resulting in dose delays and reductions, and increased utilization of healthcare services. G1 shares our organization’s goal to improve the quality of life of those diagnosed with lung cancer and to transform survivorship among people living with this insidious disease. We are thrilled to see new advancements that can help improve the lives of those living with small cell lung cancer."

Approximately 30,000 small cell lung cancer patients are treated in the United States annually. G1 is committed to helping patients with extensive-stage small cell lung cancer in the U.S. gain access to treatment with COSELA. For more information on access and affordability programs, patients and providers should call the G1toOne support center at 833-G1toONE (833-418-6663) from 8:00 a.m. to 8:00 p.m. Eastern time.

G1 received Breakthrough Therapy Designation from the FDA in 2019 based on positive data in small cell lung cancer patients from three randomized Phase 2 clinical trials. As is common with breakthrough-designated products that receive priority review, G1 will conduct certain post-marketing activities, including in vitro drug-drug interaction and metabolism studies, and a clinical trial to assess impact of trilaciclib on disease progression or survival in patients with ES-SCLC with chemotherapy-induced myelosuppression treated with a platinum/etoposide-containing or topotecan-containing regimen with at least a two year follow up. G1 intends to initiate the post-approval clinical trial in 2022.

Webcast and Conference Call
The management team will host a webcast and conference call at 8:00 a.m. ET on Tuesday, February 16, 2021 to discuss the FDA approval of COSELA (trilaciclib). The live call may be accessed by dialing 866-763-6020 (domestic) or (210) 874-7713 (international) and entering the conference code: 6195528. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

COSELA (trilaciclib) Co-Promotion Agreement with Boehringer Ingelheim

In June 2020, G1 announced a three-year co-promotion agreement with Boehringer Ingelheim for COSELA in small cell lung cancer in the U.S. and Puerto Rico. G1 will lead marketing, market access and medical engagement initiatives for COSELA. The Boehringer Ingelheim oncology commercial team, well-established in lung cancer, will lead sales force engagement initiatives. G1 will book revenue and retain development and commercialization rights to COSELA and pay Boehringer Ingelheim a promotional fee based on net sales. The three-year agreement does not extend to additional indications that G1 is evaluating for trilaciclib. Press release details of the G1/ Boehringer Ingelheim agreement can be found here.

About Small Cell Lung Cancer

In the United States, approximately 30,000 small cell lung cancer patients are treated annually. SCLC, one of the two main types of lung cancer, accounts for about 10% to 15% of all lung cancers. SCLC is an aggressive disease and tends to grow and spread faster than NSCLC. It is usually asymptomatic; once symptoms do appear, it often indicates that the cancer has spread to other parts of the body. About 70% of people with SCLC will have cancer that has metastasized at the time they are diagnosed. The severity of symptoms usually increases with increased cancer growth and spread. From the time of diagnosis, the general 5-year survival rate for people with SCLC is 6%. The five-year survival rates for limited-stage (the cancer is confined to one side of the chest) SCLC is 12% to 15%, and for extensive stage (cancer has spread to the other lung and beyond), survival rates are less than 2%. Chemotherapy is the most common treatment for ES-SCLC.

COSELA (trilaciclib) for Injection
INDICATION
COSELA is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.
WARNINGS AND PRECAUTIONS

Injection-Site Reactions, Including Phlebitis and Thrombophlebitis

COSELA administration can cause injection-site reactions, including phlebitis and thrombophlebitis, which occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions. Monitor patients for signs and symptoms of injection-site reactions, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after end of infusion. For severe (Grade 3) or life-threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue COSELA. Injection-site reactions led to discontinuation of treatment in 3 (1%) of the 272 patients.
Acute Drug Hypersensitivity Reactions

COSELA administration can cause acute drug hypersensitivity reactions, which occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%). Monitor patients for signs and symptoms of acute drug hypersensitivity reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold COSELA until the adverse reaction recovers to Grade ≤1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue COSELA.
Interstitial Lung Disease/Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK)4/6 inhibitors, including COSELA, with which it occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials. Monitor patients for pulmonary symptoms of ILD/pneumonitis. For recurrent moderate (Grade 2) ILD/pneumonitis, and severe (Grade 3) or life-threatening (Grade 4) ILD/pneumonitis, permanently discontinue COSELA.
Embryo-Fetal Toxicity

Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose.
ADVERSE REACTIONS

Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis.

Fatal adverse reactions were observed in 5% of patients receiving COSELA. Fatal adverse reactions for patients receiving COSELA included pneumonia (2%), respiratory failure (2%), acute respiratory failure (<1%), hemoptysis (<1%), and cerebrovascular accident (<1%).

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received COSELA. Adverse reactions leading to permanent discontinuation of any study treatment for patients receiving COSELA included pneumonia (2%), asthenia (2%), injection-site reaction, thrombocytopenia, cerebrovascular accident, ischemic stroke, infusion-related reaction, respiratory failure, and myositis (<1% each).

Infusion interruptions due to an adverse reaction occurred in 4.1% of patients who received COSELA.

The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.
DRUG INTERACTIONS

COSELA is an inhibitor of OCT2, MATE1, and MATE-2K. Co-administration of COSELA may increase the concentration or net accumulation of OCT2, MATE1, and MATE-2K substrates in the kidney (e.g., dofetilide, dalfampridine, and cisplatin).
To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.