On March 29, 2021 Tempest Therapeutics, Inc. ("Tempest"), a privately-held clinical-stage oncology company developing potentially first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, and Millendo Therapeutics, Inc. (Nasdaq: MLND) ("Millendo"), reported that they have entered into a definitive agreement under which Millendo will merge with Tempest in an all-stock transaction (Press release, Tempest Therapeutics, MAR 29, 2021, View Source [SID1234577287]). The combined company will focus on advancing Tempest’s oncology pipeline of small molecule therapeutics that have the potential to address a wide range of tumors. Upon shareholder approval, the combined company is expected to operate under the name Tempest Therapeutics and trade on the Nasdaq Capital Market under the ticker symbol TPST.

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In support of the merger, Tempest has secured commitments from a premier syndicate of healthcare investors comprised of Versant Ventures, Rock Springs Capital, F-Prime Capital, Monashee Investment Management, Quan Capital, Lyfe Capital, Maven Investment Partners US, Lilly Asia Ventures and Eight Roads Ventures for a $30 million PIPE financing that is expected to close concurrent with the completion of the merger. Together with the cash expected from both companies at closing, the net proceeds of the merger and financing are expected to fund the further development of Tempest’s three oncology programs and operate the company into early 2023. The financing and merger are expected to close in the first half of 2021.

"We are very pleased to announce this proposed merger with Millendo Therapeutics, which will facilitate the advancement of our broad pipeline of targeted oncology programs, including TPST-1495 and TPST-1120, which are both progressing in the clinic with encouraging early signs of clinical benefit," said Tom Dubensky, Ph.D., chief executive officer of Tempest. "Together with our recently announced clinical collaboration with Roche to investigate TPST-1120 in a randomized frontline hepatocellular carcinoma study, this has been a highly productive quarter for Tempest that sets the stage for additional potential catalysts from our proprietary oncology programs. The transition of Tempest to a public company enhances our ability to fund these potentially important product candidates, as well as consider additional programs with exciting new targets."

Tempest’s oncology pipeline is led by two clinical programs, TPST-1495 and TPST-1120, with broad potential across multiple tumor types. TPST-1495 is an antagonist selective for two receptors in the prostaglandin (PGE2) pathway, EP2 and EP4, which promote both tumor growth and the proliferation of suppressive immune cell populations. Tempest is currently evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of TPST-1495 in a multicenter Phase 1a/1b dose and schedule optimization study in patients with advanced solid tumors, with a focus on known prostaglandin-driven tumors such as colorectal cancer, lung adenocarcinoma and urothelial cancer. Tempest expects to report topline data from this study prior to the end of 2021, as well as data from planned monotherapy dose expansion and combination studies in 2022. TPST-1120 is designed to be a selective antagonist of proliferator-activated receptor alpha (PPAR⍺) which is a transcription factor that regulates the expression of target genes that promote angiogenesis and enable a cellular metabolic pathway known as fatty acid oxidation. TPST-1120 has completed monotherapy dose escalation and is progressing through a combination dose escalation study with nivolumab. This summer, Tempest expects F. Hoffmann-La Roche Ltd to initiate a global, randomized Phase 1b/2 clinical study in combination with the standard-of-care first-line regimen of atezolizumab and bevacizumab in patients with advanced or metastatic HCC not previously treated with systemic therapy, pursuant to a recently announced collaboration between the companies. Tempest expects to report topline data from this study by year-end 2022.

"Millendo Therapeutics’ strategic review was a thorough and thoughtful process. We believe we have found a partner that offers not only the greatest value for our existing shareholders but also promising targeted oncology product candidates for patients living with cancer," said Louis Arcudi, chief executive officer of Millendo.

About the Proposed Merger

Millendo stockholders are expected to own approximately 18.5% of the combined company and pre-merger Tempest stockholders will own approximately 81.5% of the combined company. The percentage of the combined company that Millendo’s stockholders will own as of the close of the transaction is subject to adjustment based on the amount of Millendo’s net cash at the closing date.

Upon closing of the transaction, Millendo will be renamed Tempest Therapeutics, Inc. and will be headquartered in South San Francisco, CA. Stephen Brady and Tom Dubensky, Ph.D., will serve as chief executive officer and president, respectively, of the combined company. The merger agreement provides that the Board of Directors of the combined company will be comprised of seven members. The merger agreement has been approved by the Board of Directors of each company, and the transaction is expected to close in the first half of 2021, subject to approvals by the stockholders of each company, the effectiveness of a registration statement filed with the U.S. Securities and Exchange Commission to register the shares of Millendo common stock to be issued in connection with the merger, the completion of a PIPE financing, and other customary closing conditions.

SVB Leerink is serving as the exclusive financial advisor to Millendo and WilmerHale is serving as legal counsel. Piper Sandler is serving as the exclusive financial advisor to Tempest and Sidley Austin is serving as legal counsel.

Conference Call Information

Millendo and Tempest will host a conference call today, March 29, 2021, at 8:30 a.m. ET, to discuss the merger. The conference call may be accessed by dialing 1-(678) 302-3550 or 1-(866) 939-3921 internationally and referencing conference ID number 50135737. A live webcast of the presentation will be available on the Investors & Media section of Millendo’s website at View Source and Tempest’s website at www.tempesttx.com. A replay of the webcast will be archived on both company’s websites for 30 days following the presentation.

On March 29, 2021 AVEO Oncology (Nasdaq: AVEO) reported that the National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines to include FOTIVDA (tivozanib) as a recommended regimen for subsequent therapy (Press release, AVEO, MAR 29, 2021, View Source [SID1234577286]). The subsequent therapy category follows the first-line treatment regimen recommendations for patients with clear cell histology renal cell carcinoma (ccRCC). On March 10, 2021, the U.S. Food and Drug Administration (FDA) approved FOTIVDA for the treatment of adults with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI).

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"FOTIVDA’s addition to the NCCN Guidelines provides further validation for its potential to serve as an important evidence-based, well tolerated treatment option for patients with relapsed or refractory advanced RCC," said Michael Bailey, president and chief executive officer of AVEO. "As previously announced, launch efforts are now underway, and we are committed to bringing this promising therapy to as many appropriate patients as possible."

The NCCN Clinical Practice Guidelines are the recognized standard for clinical policy in cancer care and are developed through review of evidence and recommendations from physicians and oncology researchers. The current NCCN RCC guidelines categorically make treatment recommendations for first-line or subsequent therapy options for RCC patients. FOTIVDA is now recommended by the NCCN Guidelines as a subsequent therapy for patients with ccRCC who have received two or more prior systemic therapies (Category 2a). FOTIVDA’s addition to the NCCN Guidelines follows its recent U.S. FDA approval, which was based on AVEO’s pivotal Phase 3 study, TIVO-3, comparing FOTIVDA to sorafenib in relapsed or refractory advanced RCC following two or more prior systemic therapies. The approval was also supported by three additional trials in RCC and included safety data from over 1,000 clinical trial subjects.

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models1. FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.

Females and Males of Reproductive Potential: Can impair fertility.

Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

On March 29, 2021 AntiCancer Inc. reported that its patent application on oral methioninase has been allowed by the United States Patent and Trademark Office (USPTO) (Press release, AntiCancer, MAR 29, 2021, View Source [SID1234577285]). Oral methioninase in preclinical studies has shown efficacy against cancer of all types, and against diabetes, obesity and fatty liver. It is also predicted to have efficacy against Covid-19. All of these diseases require the amino acid methionine in abnormally high amounts. Oral methioninase acts against these diseases by restricting methionine in the body.

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"Methioninase is safe since it can be taken orally," said Dr. Qinghong Han, head of oral methioninase development at AntiCancer and an inventor on the new patent. "Oral methioninase acts by drastically restricting methionine in the digestive system. It has tremendous commercial potential, as it is active against diseases such as cancer, diabetes, and Covid-19, which all require an elevated amount of methionine. Just as exciting, oral methioninase also has the potential to inhibit aging."

AntiCancer has spun out a wholly-owned subsidiary Methuselah Pharmaceuticals LLC to commercialize methioninase. "The new patent will enable AntiCancer and Methuselah to uniquely market methioninase," said Dr. Han.

AntiCancer Inc. uniquely also offers patient-derived orthotopic xenograft (PDOX) mouse models, which most closely resemble the cancer patient. AntiCancer also offers HDRA 3-dimensional tumor culture for cancer drug discovery and evaluation. Anticancer is also developing tumor- targeting bacteria; pluripotent hair follicle stem cells which form neurons and other cell types for regenerative medicine and has pioneered tumor-specific fluorescence-guided surgery.

On March 29, 2021 SCYNEXIS, Inc. (NASDAQ: SCYX), a biotechnology company pioneering innovative medicines to overcome and prevent difficult-to-treat and drug-resistant infections, reported financial results for the fourth quarter ended on December 31, 2020 and provided an update on recent clinical and corporate developments (Press release, Scynexis, MAR 29, 2021, View Source [SID1234577284]).

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"This has been an extremely active period for our team as we build out the commercial infrastructure in preparation for the anticipated approval of Brexafemme for vaginal yeast infections on June 1, 2021, while advancing the hospital clinical programs in both the oral and IV formulations," said Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS. "Between our successful $85 million public offering in December and our recent $10 million upfront payment in connection with our partnership with Hansoh Pharma in the Greater China region, we have also fortified our balance sheet, with our cash runway projected into 2023."

Ibrexafungerp Update

SCYNEXIS announced on December 7, 2020 that its NDA for oral ibrexafungerp for the treatment of vulvovaginal candidiasis (VVC), also known as vaginal yeast infection, was accepted for filing by the U.S. Food and Drug Administration (FDA). The FDA has granted this application Priority Review and set a Prescription Drug User Fee Act (PDUFA) target action date of June 1, 2021. Additionally, the FDA has communicated that it is not currently planning to hold an advisory committee meeting to discuss the application.

Enrollment is complete in the Phase 3 CANDLE study, investigating the efficacy and safety of oral ibrexafungerp for the prevention of recurrent VVC, for which there is no approved therapy in the U.S. SCYNEXIS expects the last-patient / last-visit by the end of 2021 with top-line results and a supplemental NDA submission anticipated in the first half of 2022, resulting in a potential approval in late 2022.

Enrollment is ongoing in SCYNEXIS’s refractory invasive fungal infections (rIFI) program, which comprises two open-label Phase 3 studies (FURI and CARES). On March 2, 2021 SCYNEXIS presented positive data from its third interim analysis of the FURI study and first interim analysis of the CARES study, showing oral ibrexafungerp’s ability to treat severe fungal infections in the hospital setting. Consistent with two prior interim analyses, the FURI results confirm positive clinical activity of oral ibrexafungerp in patients with difficult-to-treat, severe, mucocutaneous and invasive fungal infections, including those caused by resistant strains. In total, oral ibrexafungerp showed clinical benefits in 64 out of 74 patients (86.5%), with 46 patients achieving a complete or partial response and 18 patients with stable disease. The first interim analysis of CARES study showed strong clinical activity of oral ibrexafungerp in patients with invasive candidiasis and candidemia due to Candida auris, a high-mortality infection classified by Centers for Disease Control and Prevention (CDC) as an urgent threat to public health, with 8 out of 10 patients (80.0%) experiencing a complete response. The results support continued enrollment in both open-label Phase 3 studies, with potential future submissions under the LPAD regulatory pathway.

Dosing is ongoing in Phase 1 testing of the liposomal IV formulation of ibrexafungerp. Based on promising pre-clinical data of SCYNEXIS’s liposomal IV formulation of ibrexafungerp, SCYNEXIS is conducting a Phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of the IV liposomal formulation of ibrexafungerp in healthy subjects. The study is being conducted in South Africa and dosing started in March 2021.

Enrollment is ongoing in the Phase 2 SCYNERGIA study for patients with invasive aspergillosis. SCYNERGIA is evaluating oral ibrexafungerp in combination with voriconazole for the treatment of patients with this high-mortality infection. Top-line data from this study is expected by the end of 2021.
Corporate Developments and Subsequent Events

On December 2, 2020, SCYNEXIS amended its license agreement with Merck, eliminating two cash milestone payments that it would have paid to Merck upon the first filing of an NDA and first marketing approval in the U.S., anticipated in June 2021 for SCYNEXIS’s NDA for ibrexafungerp for the treatment of VVC. Such cash milestone payments would have been creditable against future royalties owed to Merck on net sales of ibrexafungerp. With the amendment, these milestones will not be paid in cash and, accordingly, credits will not accrue. SCYNEXIS will also forfeit the credits against future royalties that it had accrued from a prior milestone payment already paid to Merck.

On December 22, 2020, SCYNEXIS announced the closing of an $85 million public offering of common stock, prefunded warrants and warrants.

On February 11, 2021, SCYNEXIS entered into a licensing and strategic partnership agreement for ibrexafungerp with Hansoh Pharmaceutical that covers the Greater China region. SCYNEXIS received a $10 million upfront payment and is eligible to receive development and commercial milestone payments of up to $112 million, plus low double-digit royalties on net sales.

On February 23, 2021, SCYNEXIS announced that it has partnered with Amplity Health, a leading global contract commercialization organization, to support the anticipated U.S. commercialization of Brexafemme, the conditionally FDA-approved brand name for ibrexafungerp for vaginal yeast infections, in the second half of 2021. SCYNEXIS will utilize Amplity’s commercial execution expertise and resources for sales force, remote engagement, training, market access and select operations services.
Full Year 2020 Financial Results

Cash and cash equivalents totaled $93.0 million as of December 31, 2020, compared to $48.4 million in cash, cash equivalents, and short-term investments at December 31, 2019.

Research and development expense for the year ended December 31, 2020 decreased to $36.5 million from $38.4 million for the year ended December 31, 2019. The decrease of $1.9 million, or 4.9%, was primarily driven by a milestone payment made in 2019 to Merck upon initiation of the Phase 3 VVC registration study, a decrease of $4.2 million in clinical development expense, a decrease of $1.0 million in preclinical expense, offset in part by an increase of $4.5 million in chemistry, manufacturing, and controls (CMC), an increase of $1.1 million in salary and consulting related costs, an increase of $1.1 million in regulatory expense, and a net increase in other research and development expense of $0.6 million.

Selling, general and administrative expenses for the year ended December 31, 2020 increased to $14.6 million from $10.6 million for the year ended December 31, 2019. The increase of $4.0 million, or 37.4%, was primarily driven by a $1.5 million increase in commercial and business development expense, a $1.3 million increase in other professional service expense, a $0.9 million increase in salary and other compensation related costs, and a net increase in other selling, general and administrative expenses of $0.3 million.

Total other expense was $7.2 million for the year ended December 31, 2020, compared to total other expense of $4.8 million for the year ended December 31, 2019. During the year ended December 31, 2020 and 2019, SCYNEXIS recognized non-cash expenses of $5.2 million and $4.5 million, respectively, on the fair value adjustment of the warrant liabilities and during the year ended December 31, 2020 and 2019, recognized non-cash gains of $2.3 million and $1.6 million on the fair value adjustment of the derivative liabilities, respectively.

Net loss for the year ended December 31, 2020 was $55.2 million, or ($5.15) per basic and diluted share, compared to a net loss of $53.7 million, or ($9.58) per basic and diluted share for the year ended December 31, 2019.

About Ibrexafungerp

Ibrexafungerp [pronounced eye-BREX-ah-FUN-jerp] is an investigational antifungal agent and the first representative of a novel class of structurally-distinct glucan synthase inhibitors, triterpenoids. This agent combines the well-established activity of glucan synthase inhibitors with the potential flexibility of having oral and intravenous (IV) formulations. Ibrexafungerp is currently under regulatory review for the treatment of vaginal yeast infection, also known as vulvovaginal candidiasis (VVC), and in late-stage development for multiple indications, including life-threatening fungal infections caused primarily by Candida (including C. auris) and Aspergillus species in hospitalized patients. It has demonstrated broad-spectrum antifungal activity, in vitro and in vivo, against multidrug-resistant pathogens, including azole- and echinocandin-resistant strains.

The FDA has accepted a New Drug Application for ibrexafungerp for the treatment of VVC and granted a Prescription Drug User Fee Act (PDUFA) action date of June 1, 2021. It also granted Qualified Infectious Disease Product (QIDP) and Fast Track designations for the IV and oral formulations of ibrexafungerp for the indications of invasive candidiasis (IC) (including candidemia) and invasive aspergillosis (IA), and has granted Orphan Drug Designation for the IC and IA indications. Ibrexafungerp is formerly known as SCY-078.

On March 29, 2021 Onconova Therapeutics, Inc. (NASDAQ: ONTX) ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported that Steven Fruchtman, M.D., President and Chief Executive Officer, will present a Company overview and hold one-on-one meetings during the Spring 2021 Oncology Investor Conference, sponsored by the National Foundation for Cancer Research (Press release, Onconova, MAR 29, 2021, View Source [SID1234577283]).

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Event: Spring 2021 Oncology Investor Conference
Date: The virtual conference will take place March 29 to April 2, 2021
Onconova Presentation: Thursday, April 1, 2021 at 11:50 a.m. Eastern time
Conference Registration Link: View Source

A webcast of Dr. Fruchtman’s presentation will be available on the Company’s website at View Source beginning Friday, April 2nd.