On April 22, 2022 Novartis reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion and recommended granting marketing authorization of Tabrecta (capmatinib) as a monotherapy for the treatment of adults with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial-transition factor gene (MET) exon 14 (METex14) skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy (Press release, Novartis, APR 22, 2022, View Source [SID1234612866]).

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!

"Patients with alterations leading to METex14 skipping have an urgent need for treatment options, as this form of lung cancer is aggressive, often diagnosed in an advanced stage and frequently comes with a poor prognosis," said Juergen Wolf, MD, from the Center for Integrated Oncology, University Hospital Cologne, Germany, and lead investigator of the GEOMETRY mono-1 trial. "The positive CHMP opinion for Tabrecta brings an option to patients for a treatment specific to their tumor. If approved by the European Commission, new targeted therapies like Tabrecta—supported by early and broad molecular testing of patients’ tumors—can better guide treatment decisions and ensure patients receive the appropriate therapy for their cancer."

The CHMP opinion is based on results from the Phase II GEOMETRY mono-1 trial that demonstrated positive overall response rates (ORR) among adult patients with advanced NSCLC whose tumors had alterations leading to METex14 skipping1. Based on data presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, among 31 patients who received Tabrecta as second-line therapy in the METex14 skipping pretreated population, a confirmed ORR of 51.6% (95% CI, 33.1-69.8) was achieved, and the ORR across all 100 previously-treated patients, which included patients who received one or two prior lines of systemic therapy, was 44.0% (95% CI, 34.1-54.3)1. The most common treatment-related adverse events (AEs) (incidence ≥20%)were peripheral oedema, nausea, fatigue, vomiting, dyspnea, decreased appetite and back pain1.

"Every 30 seconds, someone dies of lung cancer—the need for more treatment options is critical. Through research and targeted therapies like Tabrecta, we are working to change that statistic and make a positive impact on the lives of people affected by cancer around the world," said Marie-France Tschudin, President, Innovative Medicines International & Chief Commercial Officer, Novartis. "Today’s announcement represents an important step forward for people in the European Union with previously-treated advanced NSCLC having alterations leading to METex14 skipping."

In the European Union, there are an estimated 291,000 patients with locally advanced or metastatic NSCLC5. METex14 skipping, a recognized oncogenic driver, occurs in approximately 3-4% of NSCLC cases3,4.

About Tabrecta (capmatinib)
Tabrecta (capmatinib) is approved in several countries including the US, Switzerland and Japan. It is the number one prescribed targeted therapy for patients with advanced NSCLC with alterations leading to METex14 skipping globally2.

Tabrecta is a kinase inhibitor that targets MET. Tabrecta was discovered by Incyte and licensed to Novartis in 2009. Under the agreement, Incyte granted Novartis worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.

About GEOMETRY mono-1
GEOMETRY mono-1 is a Phase II multi-center, non-randomized, open-label, multi-cohort study in adult patients with EGFR wild-type, ALK-negative rearrangement, advanced NSCLC with alterations that lead to MET exon-14 skipping who received 400 mg of capmatinib orally twice daily1.

Patients were assigned to cohorts on the basis of MET status and previous lines of therapy. The primary endpoint was overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) evaluated by BIRC1.

Mature data from the trial, including from an expansion cohort analysis, showed Tabrecta demonstrated a median duration of response of 9.7 months (95% CI, 5.6-13.0) in all previously-treated patients (n=100)1. In addition, Tabrecta demonstrated a median overall survival of 13.6 months (95% CI, 8.6-22.2) in previously-treated patients (n=69)1. The median progression-free survival was 5.5 months (95% CI, 4.2‑8.1) for all previously-treated patients (n=100) and 6.9 months (95% CI, 4.2-13.3) for patients who received Tabrecta as second-line therapy (n=31)1. The Disease Control Rate across all previously-treated patients was 82.0% (95% CI, 73.1-89.0)1. The expansion cohort analysis enrolled 160 patients with MET alterations and included previously-treated cohorts (n=100) who had been treated with one or two prior lines of systemic therapy for advanced disease, as well as treatment-naive cohorts (n=60)1.

Overall, Tabrecta demonstrated a manageable safety profile and there were no new safety signals or unexpected safety findings1. The most common treatment-related adverse events (AEs) (incidence ≥20%) were peripheral oedema, nausea, fatigue, vomiting, dyspnea, decreased appetite and back pain1.

About MET exon 14 skipping
MET (mesenchymal-epithelial transition), a receptor tyrosine kinase coded by the MET gene, normally plays an important role in cell signaling, proliferation and survival3. Many cancers are associated with abnormal signaling through the MET receptor pathway, caused by multiple mechanisms including point mutations, insertions and deletions that lead to skipping of exon 14. MET exon 14 (METex14) skipping is an oncogenic alteration in NSCLC that can result in overstimulation of the MET pathway3.

Patients with alterations that lead to METex14 skipping often have a poor prognosis due to the aggressiveness of the cancer and limited treatment options6-8.

Novartis and lung cancer
The needs in lung cancer are urgent and significant. Each year, more than 2 million people are newly diagnosed globally, and lung cancer remains the number one cause of cancer-related death worldwide9. There are two main types of lung cancer—small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of lung cancer diagnoses10.

Novartis is making bold investments in advancing the science to drive treatment and make an impact for patients around the world. The company is committed to working with the scientific and medical communities to reimagine the treatment of lung cancer and pursue advances in medicine that could extend the survival of people living with lung cancer.

With one of the most diverse lung cancer development programs in the industry, Novartis is developing therapies that block cancer growth; learning more about ways to activate the body’s immune system; increasing understanding of the relationship between unregulated inflammation and tumor growth and recurrence; and exploring the potential for advanced nuclear medicine to fight the disease. Through these programs, Novartis aims to redefine possibilities in lung cancer and pursue a trajectory to make lung cancer history.

On April 22, 2022 Savara Inc. (Nasdaq: SVRA), a clinical stage biopharmaceutical company focused on rare respiratory diseases, reported that it entered into a term loan agreement of $26.5 million with Silicon Valley Bank to replace its existing credit facility with the bank (Press release, Savara, APR 22, 2022, View Source [SID1234612865]). The new facility represents a significant improvement in economic terms, including a lower interest rate compared to the existing loan rate and an initial 48-month interest only period.

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 are pleased to continue our partnership with Silicon Valley Bank as this strategic refinancing meaningfully reduces our cost of capital, strengthens our balance sheet, and provides increased flexibility as we continue to advance the development program for our inhaled biologic, molgramostim nebulizer solution," said Matt Pauls, Chair and CEO, Savara. "With a cash position of ~$161M at the end of 2021, we believe we are funded through 2025 – which is well beyond the anticipated top line read-out of IMPALA-2, our pivotal Phase 3 clinical trial of molgramostim in autoimmune pulmonary alveolar proteinosis."

Under the terms of the agreement, $26.5 million was funded upon execution of the agreement, which will be used to repay Savara’s existing credit facility. The new credit facility bears an interest rate of the greater of prime minus 0.50% or 3% and has a maturity of 5 years. The initial 48 monthly payments will be interest only, followed by 12 monthly payments of principal and accrued interest. There are no warrants in connection with the agreement.

On April 22, 2022 This weekend, Madrid is hosting the "Generating Evidence and Sharing Experience (GESE)" Congress, organized by PharmaMar (MSE:PHM), reported that where leading European oncologists and medical specialists will meet to share the latest advances in the treatment and diagnosis of this disease (Press release, PharmaMar, APR 22, 2022, View Source [SID1234612864]).

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!

Soft Tissue Sarcoma (STS) is a group of solid tumors that can develop anywhere in the body, forming in soft tissues such as cartilage, fat, muscle, nerves, blood vessels or the deep tissues of the skin. Although STS can occur anywhere in the body, it usually occurs (43%) in the arms and legs.

Sarcoma is a type of cancer that encompasses more than 60 different subtypes. They are rare tumors that can appear at any time in life. Within localized sarcomas, the probability of survival, with appropriate treatment, is around 65% to 70%. This heterogeneity makes it difficult for specialists to decide on the treatment to combat the disease.

The attendees, experts from France, Italy, Germany, Austria, Holland, Switzerland, Portugal and Spain, will address topics such as the most avant-garde options for treatment, ultra-rare pathologies, new combinations, and the patient’s quality of life as an essential issue in the evolution of sarcomas, among others.

STS is one of the most difficult tumors to treat. Not only because of the difficulty required for its diagnosis -where the patient plays a very important role- but also because there are several different professionals who must deal with the treatment of these tumors in a multi-disciplinary manner.

On April 22, 2022 Orion’s collaboration partner Bayer reported the submission of a regulatory application to the Center of Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), for the oral androgen receptor inhibitor (ARi) darolutamide (Press release, Orion , APR 22, 2022, View Source [SID1234612863]). Bayer is seeking approval for the use of darolutamide for the treatment of adult patients with metastatic hormone sensitive prostate cancer (mHSPC) in combination with docetaxel. The compound is already approved under the brand name Nubeqa for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease, in more than 60 markets around the world, including the U.S., the European Union (EU), Japan and China.

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 CDE submission is supported by positive results from the Phase III ARASENS trial, showing a statistically significant improvement in overall survival (OS) for darolutamide plus androgen deprivation therapy (ADT) and docetaxel in men with mHSPC. These results were presented in February at the 2022 ASCO (Free ASCO Whitepaper) GU Cancers Symposium and simultaneously published in The New England Journal of Medicine.

Darolutamide is developed jointly by Orion and Bayer. Additional submissions in mHSPC are planned by Bayer globally. The compound is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE) as well as an ANZUP-led international co-operative group Phase III trial, evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP, ANZUP1801).

About the ARASENS Trial

The ARASENS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the efficacy and safety of oral darolutamide, an androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, plus ADT and docetaxel.

The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all measured at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability.

About Metastatic Hormone-Sensitive Prostate Cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.1

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 5% of men will already suffer from prostate cancer with distant metastases when first diagnosed. Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of the chemotherapy docetaxel and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.

About darolutamide

Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. A low blood-brain barrier penetration would explain the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial and the improved verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.

The product is approved under the brand name Nubeqa in more than 60 markets around the world, including the U.S., EU, Japan, China, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. The compound is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE) as well as an ANZUP-led international co-operative group Phase III trial, evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP, ANZUP1801). Information about these trials can be found at www.clinicaltrials.gov.

On April 22, 2022 SCYNEXIS, Inc. (Nasdaq: SCYX) reported that the pricing of its underwritten public offering of common stock, pre-funded warrants and warrants (Press release, Scynexis, APR 22, 2022, View Source [SID1234612845]). The shares and warrants are being sold at a public offering price of $3.00 per share and accompanying warrants, and the pre-funded warrants are being sold at a public offering price of $2.999 per pre-funded warrant and accompanying warrants. The gross offering proceeds to SCYNEXIS from this offering are expected to be approximately $45.0 million, before deducting the underwriting discount and other estimated offering expenses, and excluding the exercise of any pre-funded warrants or warrants. All of the shares of common stock, pre-funded warrants and warrants are being offered by SCYNEXIS.

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!

At closing, SCYNEXIS will issue 3,333,333 shares of its common stock, pre-funded warrants to purchase an aggregate of 11,666,667 shares of common stock and warrants to purchase an aggregate of 15,000,000 shares of its common stock. The pre-funded warrants will be issued to certain purchasers who have elected to purchase them in lieu of shares of common stock in this offering, as those purchasers would otherwise have exceeded 19.99% (or such lesser percentage as required by the investor) beneficial ownership of our common stock immediately following the offering. The shares of common stock, pre-funded warrants and warrants will be issued separately. The warrants have a seven-year term and an exercise price of $3.45 per share. The pre-funded warrants and the warrants are exercisable immediately upon issuance. The warrants will be certificated and will be delivered to the investors by physical delivery following the closing. There is no established public trading market for the pre-funded warrants or the warrants, and SCYNEXIS does not expect a market to develop.

In addition, SCYNEXIS has granted the underwriters a 30-day option to purchase up to an additional 2,250,000 shares of common stock and/or warrants to purchase up to 2,250,000 shares of common stock, at their respective public offering prices, less the underwriting discounts and commissions.

Guggenheim Securities, LLC and Cantor Fitzgerald & Co. are serving as joint book-running managers for the offering. Ladenburg Thalmann & Co. Inc. and Maxim Group LLC are serving as co-lead managers for the offering. Aegis Capital Corp, Brookline Capital Markets, a division of Arcadia Securities, LLC, and WBB Securities LLC are serving as co-managers for the offering.

A shelf registration statement relating to the securities being sold in this offering was filed with the U.S. Securities and Exchange Commission (the "SEC") on December 31, 2020, and was declared effective on January 8, 2021. The offering will be made only by means of a preliminary and final prospectus supplement and accompanying prospectus. When available, copies of the preliminary and final prospectus supplements and accompanying prospectus relating to the proposed public offering may be obtained by contacting: Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, New York 10017, or by telephone at (212) 518-9544 or by email at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 4th Floor, New York, New York 10022, or by email at [email protected]. The final terms of the offering will be disclosed in the final prospectus supplement to be filed with the SEC.

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.