On May 6, 2021 Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, and Amplitude Healthcare Acquisition Corporation (Nasdaq: AMHCU), a special purpose acquisition company (SPAC) sponsored by affiliates of Avego Management, LLC and Metalmark Capital, reported they have entered into a definitive business combination agreement (Press release, Jasper Therapeutics, MAY 6, 2021, View Source [SID1234579421]). Upon closing of the transaction, anticipated to occur in the third quarter 2021, the combined company will be renamed Jasper Therapeutics, Inc., and its common stock is expected to be listed on Nasdaq under the ticker symbol "JSPR ."

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"We would like to thank our financial partners at Amplitude and our prestigious group of investors," said Bill Lis, executive chairman and CEO, Jasper Therapeutics. "This transaction provides significant capital to accelerate the development of our two innovative programs, Jasper’s first-in-class clinical stage anti-CD117 antibody transplant conditioning agent and in parallel our groundbreaking research stage Engineered Hematopoietic Stem Cell platform, both of which have the potential to transform the field and expand hematopoietic stem cell therapy cures to a far greater number of patients than is possible today."

"At Jasper we are focused on a mission to cure several life threatening diseases such as blood cancers, sickle cell disease, severe combined immunodeficiency, and severe autoimmune diseases that affect a large number of patients who have historically been underserved by industry research and development, including infants, women, minorities and the elderly."

In addition to the funds held in Amplitude’s trust account (approximately $100 million less any redemptions), the transaction also includes commitments for a $100 million private investment in public equity (PIPE) priced at $10.00 per share. Investors in the PIPE include lead investor Federated Hermes Kaufmann Funds and affiliates of the SPAC sponsor including Avego, Velan Capital and Metalmark, as well as Amgen, Christian Angermayer’s Apeiron Investment Group, Kingdon Capital Management, and Woodline Partners LP, in addition to existing Jasper investors Abingworth LLP, Qiming Venture Partners USA, Surveyor Capital (a Citadel company), Roche Venture Fund and Alexandria Venture Investments, LLC. Jasper Therapeutics is expected to have cash resources of approximately $180 million at the closing of the transaction (less any redemptions from the Amplitude trust account).

The boards of directors of both Jasper Therapeutics and Amplitude have unanimously approved the proposed transaction. Completion of the transaction, which is expected in the third quarter of 2021, is subject to approval of Amplitude’s stockholders and the satisfaction or waiver of certain other customary closing conditions.

"Jasper Therapeutics has a strong management team with deep scientific expertise in the field and a track record developing and commercializing novel drugs, along with a pipeline that could make it a formidable leader in hematopoietic stem cell transplantation for a broad range of indications," said Vishal Kapoor, President of Amplitude. "When Jasper Therapeutics emerges as a public company, it will be positioned as a well-funded leader in hematopoietic stem cell conditioning and engineering, an area that has seen far too little innovation."

Jasper Therapeutics expects to use the cash resources of the combined company following the merger and PIPE to support the clinical development of JSP191, a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow, creating an empty space for donor or gene-corrected transplanted stem cells to engraft. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients. It is currently enrolling in two clinical trials for acute myeloid leukemia (AML)/ myelodysplastic syndromes (MDS) and severe combined immunodeficiency (SCID) and is scheduled to begin enrollment in 3 additional studies in 2021 for severe autoimmune disease, sickle cell disease and Fanconi anemia patients undergoing hematopoietic cell transplantation.

Jasper Therapeutics also expects to use the cash resources of the combined company to continue to advance its preclinical Engineered Hematopoietic Stem Cell (eHSCs) platform, which is designed to overcome key limitations of allogeneic and autologous gene-edited stem cell grafts. By using mRNA or DNA editing, Jasper Therapeutics can give the donor or gene-edited stem cells a proliferative and survival advantage over the patient’s existing stem cells. Preclinical data have demonstrated that Jasper’s eHSCs grow faster and outcompete normal hematopoietic stem cells and that they can be engineered to become resistant to inhibition by JSP191, suggesting that they could be combinable as a conditioning and therapeutic pair.

Transaction Overview

Assuming a share price of $10.00 per share and no redemptions of Amplitude shares, Jasper Therapeutics is expected to have an initial market capitalization of approximately $490 million dollars. Upon the closing of the business combination, and assuming no redemptions of shares of Amplitude by its public stockholders, Jasper Therapeutics is expected to have cash resources of approximately $180 million at the closing of the transaction (less any redemptions). The proceeds will be funded through a combination of approximately $100 million cash in trust by Amplitude (less any redemptions from its trust account) and a $100 million concurrent PIPE of common stock issued at $10.00 per share, anchored by leading institutional investors. As part of the transaction, Jasper Therapeutics’ existing equity holders will roll 100% of their equity into the combined company.

The boards of directors of both Jasper Therapeutics and Amplitude have unanimously approved the proposed transaction, which is expected to be completed in the third quarter of 2021. The transaction is subject to, among other things, the approval of the stockholders of both Jasper Therapeutics and Amplitude, satisfaction or waiver of the conditions stated in the definitive business combination agreement.

Additional information about the transaction will be provided in a Current Report on Form 8-K to be filed by Amplitude with the SEC and will be available at the SEC’s website at www.sec.gov. In addition, Amplitude intends to file a registration statement on Form S-4 with the SEC, which will include a proxy statement/prospectus, and will file other documents regarding the proposed transaction with the SEC.

Advisors

Credit Suisse is acting as lead PIPE placement agent and capital markets advisor to Jasper Therapeutics, William Blair is acting as co-placement agent and financial advisor and Cantor Fitzgerald as co-placement agent. Paul Hastings LLP is serving as legal counsel to Jasper Therapeutics. BMO Capital Markets and Oppenheimer & Co. Inc. are acting as capital markets advisors to Amplitude. Wilmer Cutler Pickering Hale and Dorr LLP is serving as legal counsel to Amplitude.

Webcast

The management team of Jasper Therapeutics will host a webcast on Friday, May 7 at 10:00 am ET to provide a brief overview of Jasper and the proposed merger. The webcast can be accessed here: View Source

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The company’s lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplantation. This first-in-class conditioning antibody is designed to enable safer and more effective curative hematopoietic cell transplants and gene therapies. Jasper Therapeutics is also advancing the development of a novel hematopoietic stem cell engineering platform.

On May 6, 2021 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reported its first quarter 2021 financial results and highlights (Press release, Synta Pharmaceuticals, MAY 6, 2021, View Source [SID1234579443]).

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"We expect several important events for Madrigal to occur in 2021," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal. "These include completing enrolling a sufficient number of subjects into the MAESTRO-NASH 52-week, serial liver biopsy population, which we expect to accomplish by the end of the second quarter, to support a future application for accelerated approval to FDA; we also expect to release topline 52 week data from the blinded arms of MAESTRO-NAFLD-1 by the end of the year."

Dr. Friedman continued, "As the competitive landscape has evolved in the sector, we believe Madrigal has emerged as a leader in the race to develop and commercialize a drug to treat NASH."

Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, "We expect the open label arms of MAESTRO-NAFLD-1 will continue to generate compelling results, including data from open label patients treated with resmetirom for 52 weeks that we hope to present at major medical conferences this year."

Dr. Taub continued, "We are enthusiastic about the growing data set from leading researchers and clinical investigators to support generally accepted, noninvasive diagnostic approaches to identify and monitor patients with NASH and significant liver fibrosis."

Financial Results for the Three Months Ended March 31, 2021
As of March 31, 2021, Madrigal had cash, cash equivalents and marketable securities of $307.2 million, compared to $284.1 million at December 31, 2020. The increase in cash and marketable securities resulted primarily from net proceeds of $66.6 million from sales of common stock via the Company’s at-the-market sales agreement, which were partially offset by cash used in operations of $43.4 million.

Operating expenses were $53.0 million for the three month period ended March 31, 2021, compared to $38.0 million in the comparable prior year period.

Research and development expenses for the three month period ended March 31, 2021 were $45.8 million, compared to $33.4 million in the comparable prior year period. The increase is attributable primarily to additional activities related to the Phase 3 clinical trials, and an increase in head count.

General and administrative expenses for the three month period ended March 31, 2021 were $7.2 million, compared to $4.6 million in the comparable prior year period. The increase in general and administrative expenses for the latest three month period is due primarily to increases in commercial preparation activities, including an increase in headcount.

Interest income for the three month period ended March 31, 2021 was $0.2 million, compared to $1.9 million in the comparable prior year period. The decrease in interest income for the latest three month period was due primarily to lower average principal balances in our investment accounts in 2021, and decreased interest rates.

About Resmetirom (MGL-3196)
Thyroid hormone, through activation of its β-receptor in hepatocytes, plays a central role in liver function impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Thyroid hormone receptor (THR)-β action in the liver is key to proper function of the liver, including regulation of mitochondrial activity such as breakdown of liver fat and control of the level of normal, healthy mitochondria. Patients with NASH have reduced levels of thyroid hormone activity in the liver with resultant impaired hepatic function, in part due to the inflamed state of the liver that causes degradation of thyroid hormone.

To exploit the thyroid hormone receptor (THR)-β pathway for therapeutic purposes in cardio-metabolic and liver diseases, it is important to avoid activity at the THR-α receptor, the predominant systemic receptor for thyroid hormone that is responsible for activity outside the liver including in heart and bone. The lack of selectivity of older thyromimetic compounds, chemically-related toxicities and undesirable distribution in the body led to safety concerns. Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-β and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-β agonism. Resmetirom has been shown to be highly selective based on 1) THR-β receptor functional selectivity based on both in vitro and in vivo assays and 2) specific uptake into the liver, its site of action, virtually avoiding any uptake into tissues outside the liver. In short and long term human and animal studies, resmetirom has been confirmed to be safe and devoid of activity at the THR-α receptor and without impact on bone or cardiac parameters. Resmetirom does not impact the thyroid axis hormones, including the central thyroid axis. Madrigal believes that resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective THR agonist.

About the Phase 3 Registration Program for the Treatment of NASH (Non-alcoholic steatohepatitis)
Analyses from the resmetirom Phase 2 NASH study demonstrate that the magnitude of liver fat reduction accurately predicts NASH resolution and liver fibrosis reduction and, specifically, that the resmetirom doses being used in Madrigal’s Phase 3 MAESTRO-NASH trial could achieve the level of fat reduction predictive of NASH resolution and fibrosis reduction [Madrigal COVID and ABSTRACT Press Release_20200414].

The Phase 3 MAESTRO-NASH trial is initially expected to enroll 900 patients with biopsy-proven NASH (fibrosis stage 2 or 3), randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. After 52 weeks of treatment a second biopsy is performed. The primary surrogate endpoint on biopsy will be NASH resolution, with at least a 2-point reduction in NAS (NASH Activity Score), and with no worsening of fibrosis. Two key secondary endpoints are liver fibrosis improvement of at least one stage, with no worsening of NASH, and lowering of LDL-cholesterol [ClinicalTrials.gov/NCT03900429].

A second 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom, MAESTRO-NAFLD-1, was initiated in December 2019 in 700 patients with non-alcoholic fatty liver disease (NAFLD), presumed NASH, randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. MAESTRO-NAFLD-1 also includes a 100 mg resmetirom open label arm in up to 100 patients. The trial was expanded to include more than 1,200 patients, in order to significantly enhance resmetirom’s safety database and provide further opportunity to study selected patient subgroups. Unlike MAESTRO-NASH, MAESTRO-NAFLD-1 is a non-biopsy study and represents a "real-life" NASH study. NASH or presumed NASH is documented using historical liver biopsy or non-invasive techniques including fibroscan and MRI-PDFF. Using non-invasive measures, MAESTRO-NAFLD-1 is designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular and liver related endpoints. These key secondary endpoints include LDL-cholesterol, apolipoprotein B and triglyceride (TG) lowering; reduction of liver fat as determined by magnetic resonance imaging, proton density fat fraction (MRI-PDFF); and reduction of PRO-C3, a NASH fibrosis biomarker. [ClinicalTrials.gov/NCT04197479] Additional secondary and exploratory endpoints will be assessed including reduction in liver enzymes, fibroscan scores and other fibrosis and inflammatory biomarkers.

These and other data, including safety parameters, form the basis for potential subpart H submission to FDA for accelerated approval for the treatment of NASH. The original 900 patients in the MAESTRO-NASH study will continue on therapy after the initial 52-week treatment period; up to another 1,100 patients are to be added using the same randomization plan and the study is expected to continue for up to 54 months to accrue and measure clinical events, most relevantly progression to cirrhosis.

About Resmetirom’s Potential to Confer Cardiovascular Risk Reduction in NASH patients
Additionally, resmetirom lowers multiple atherogenic lipids, including LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein (a), as demonstrated in Phase 2, a key differentiating factor compared with other NASH therapeutics. The magnitude of reduction of these lipids support a potential indication for treatment of hyperlipidemia in NASH patients and predicts a potential for benefit on cardiovascular (CV) events in NASH patients who die most frequently of CV, not liver disease.

Because of their diabetes, dyslipidemia, hypertension, obesity in concert with an inflamed, fatty liver, NASH patients, particularly those with advanced fibrosis, are at a substantially increased CV risk compared to the general population. Resmetirom’s ability to decrease liver fat, which is an independent risk factor for CV events, and resmetirom’s effect to reduce atherogenic lipids are being further evaluated in several key secondary endpoints in both MAESTRO Phase 3 clinical studies.

On May 6, 2021 Anavex Life Sciences Corp. ("Anavex" or the "Company") (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, reported that it will issue financial results for its fiscal quarter ended March 31, 2021 on Thursday, May 13, 2021 (Press release, Anavex Life Sciences, MAY 6, 2021, View Source [SID1234579267]).

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Management will host a conference call on Thursday, May 13, 2021 at 4:30 pm Eastern Time to review financial results and provide an update on its clinical programs and corporate highlights. Following management’s formal remarks, there will be a question-and-answer session with equity analysts.

Conference Call / Webcast Information:

The live webcast of the conference call can be accessed online at View Source

To join the conference call, live via telephone, interested parties within the U.S. should dial, toll-free, 1 (866) 866-1333 and international callers should dial 1 (404) 260-1421. Please use confirmation number 50162864, followed by the pound sign (#).

A replay of the conference call will also be available on www.anavex.com.

On May 6, 2021 Ziopharm Oncology, Inc. ("Ziopharm" or the "Company") (Nasdaq: ZIOP), reported its financial results for the first quarter ended March 31, 2021 and provided additional corporate updates (Press release, Ziopharm, MAY 6, 2021, View Source [SID1234579339]). The Company will host a conference call and webcast today at 4:30 pm ET.

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Recent Corporate Highlights and Updates

Announced that the infusion of the first patient in the CD19-Specific Rapid Personalized Manufacturing (RPM) CAR-T Phase I Clinical Trial being conducted in Taiwan by the Company’s Joint Venture partner, Eden BioCell, occurred in March.

Presented a poster entitled "Hotspot mutations in KRAS and TP53 targeted by TCR-T cells genetically modified with the Sleeping Beauty transposon/transposase system" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual 2021 Annual Meeting.

Completed construction of the GMP facility in Houston with follow on activities for facility qualification and validation to take place over the summer. The Company will then qualify the manufacturing process in the facility and file an IND amendment to enable GMP manufacturing to supplement its CMO partner’s capacity for the TCR-T hotspot trial.

Announced it is winding down its existing Controlled IL-12 clinical program. Data indicated potential clinical benefits in a variety of cancers, including recurrent glioblastoma. The Company will continue to seek a partner for this program while re-deploying resources and will explore synergies between this technology and its cell therapy programs. The Company anticipates a headcount reduction of approximately 15% related to this wind down.

Anticipate the closure of the CD19 RPM CAR-T Allogeneic Phase I Trial at MD Anderson Cancer Center. The trial closure is expected to occur during the second or third quarter of 2021.

Plans to hold its Annual Meeting of Stockholders on May 19, 2021 at 9:00 am EDT. The meeting will be held virtually. Shareholders and interested stakeholders may attend the annual meeting online using the link below. Shareholders may submit questions during the meeting and vote shares electronically during the meeting by visiting www.virtualshareholdermeeting.com/ZIOP2021.
"Our first quarter was highlighted by execution and important strategic decisions that focus our capital on our prioritized development programs," said Heidi Hagen, Chief Executive Officer of Ziopharm. "In the coming months, we are focused on delivering important milestones on our clinical trials, including our first TCR-T trial, where we plan to treat patients beginning in the second half of the year, and continued progress on the Eden BioCell CD19-specific RPM CAR-T Trial in Taiwan."

First Quarter 2021 Financial Results

Research and development expenses were $13.3 million for the first quarter of 2021, compared to $12.7 million for the first quarter of 2020, primarily reflecting increase in cell therapy program costs offset by a decrease in Controlled IL-12 program costs.

General and administrative expenses were $8.2 million for the first quarter of 2021, compared to $6.0 million for the first quarter of 2020. The increase in general and administrative expenses is primarily due to increased employee related expenses and legal costs associated with its expanded patent portfolio.

Net loss for the first quarter of 2021, was $21.6 million, or $(0.10) per share, compared to a net loss of $18.3 million, or $(0.09) per share, for the first quarter of 2020.

Cash and cash equivalents, as of March 31, 2021 were $100.1 million.

Additionally, a prepayment of approximately $5.1 million remains for work to be conducted by the Company at MD Anderson under the Company’s research and development agreements.
Earnings Conference Call and Webcast
Ziopharm will host a conference call and webcast for the investment community today, May 6, 2021, at 4:30 p.m. EDT. The conference call can be accessed by dialing 855-327-6837 (U.S. and Canada) or 631-891-4304 (International). The passcode for the conference call is 10013973. The live webcast may be accessed using the link here, or by visiting the "Investors" section of the Ziopharm website at www.ziopharm.com. The call will be recorded and available for replay on the Company’s website for approximately 90 days after the call.

Annual Meeting of Stockholders
Ziopharm will host its annual meeting virtually on May 19, 2021 at 9:00 am. Shareholders and interested stakeholders may attend the meeting, submit questions, and vote their shares electronically during the meeting by visiting www.virtualshareholdermeeting.com/ZIOP2021.

On May 6, 2021 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of drugs to treat severe metabolic, oncologic and neuropsychiatric disorders by modulating the effects of the stress hormone cortisol, reported its results for the quarter ended March 31, 2021 (Press release, Corcept Therapeutics, MAY 6, 2021, https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-provides-clinical-update-and-announces [SID1234579355]).

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First quarter 2021 revenue was $79.4 million, compared to $93.2 million in the first quarter of 2020. The decrease in revenue in the first quarter was primarily due to the effects of the COVID-19 pandemic on our business.

First quarter operating expenses were $59.8 million, compared to $55.5 million in the first quarter of 2020, due to increased spending on clinical trials in Cushing’s syndrome and metabolic diseases and the formulation and manufacture of the company’s proprietary selective cortisol modulators.

First quarter 2021 GAAP net income was $23.5 million, compared to $30.1 million in the first quarter of 2020. Excluding non-cash expenses related to stock-based compensation and the utilization of deferred tax assets, together with related income tax effects, non-GAAP net income in the first quarter was $25.8 million, compared to $41.2 million in the first quarter of 2020. A reconciliation of GAAP to non-GAAP net income is included below.

Cash and investments were $454.8 million at March 31, 2021, compared to $476.9 million at December 31, 2020. The company repurchased 2.1 million shares of its common stock in the first quarter – 1.3 million shares for $33.5 million pursuant to the company’s stock repurchase program and 0.8 million shares for $16.4 million in connection with the net exercise of stock options – at a total cost of $50.0 million. Under the stock repurchase program’s currently authorized terms, $156.8 million remains available for the purchase of shares.

Corcept modified its 2021 revenue guidance to $355 – $385 million. Corcept anticipates positive cash flow for the foreseeable future.

"The lingering effects of the spike in COVID-19 in the fourth quarter of last year extended further into the first quarter than we anticipated, coloring our commercial results," said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. "Many physicians are still not able to see their patients often enough to optimally diagnose and treat a complex disease such as Cushing’s syndrome. Further, many patients introduced to Korlym during the pandemic have so far not reached their ideal dose, as many physicians are seeing their patients less frequently, particularly in person, and testing them less frequently, slowing optimal titration.

"We expect these effects to diminish as COVID restrictions and fears diminish. The best treatment for Cushing’s syndrome involves substantial and frequent engagement between patients and physicians," said Dr. Belanoff. "Our modified 2021 revenue guidance assumes that pandemic-related obstacles will ease substantially in the third quarter – about two quarters later than we had originally thought. Leading physicians increasingly believe that the number of patients with hypercortisolism is substantially greater than once assumed. Korlym is an excellent treatment for hypercortisolism. Relacorilant, if approved, will be even better. We expect significant revenue growth and profits in the years ahead."

Clinical Development Highlights

"Despite having to contend with pandemic-related headwinds," said Dr. Belanoff, "our clinical development efforts, particularly in the United States, gained momentum in the first quarter. Today we announced positive data related to two of our proprietary, selective cortisol modulators as possible treatments for platinum-resistant ovarian cancer and NASH. These are important advances for the potential treatment of these diseases, which have a high unmet need. In addition, we are encouraged that these results provide further clinical validation of our cortisol modulation platform as a treatment for a broad range of diseases. In contrast to the past when sometimes a year would pass between releases of clinical results, we now expect important information to emerge every quarter."

Solid Tumors

In a 178-patient, controlled, Phase 2 trial, women with platinum-resistant ovarian cancer who received relacorilant plus nab-paclitaxel experienced improved progression free survival (PFS) compared to women who received nab-paclitaxel alone, with comparable safety and tolerability *
Planning underway for a Phase 3 pivotal trial in ovarian cancer
Preliminary results in the first 40 patients enrolled in open-label Phase 3 RELIANT trial of relacorilant
plus nab-paclitaxel in patients with metastatic pancreatic cancer expected this quarter
Selection of the optimum dose of exicorilant plus enzalutamide in patients with castration-resistant prostate cancer ("CRPC") expected by third quarter 2021
Enrollment continues in a 20-patient, open-label, Phase 1b trial of relacorilant plus PD-1 checkpoint inhibitor pembrolizumab in patients with adrenal cancer with cortisol excess
"We are extremely pleased with the results of our trial of relacorilant as a possible treatment for platinum-resistant ovarian cancer," said Andreas Grauer, MD, Corcept’s Chief Medical Officer. "Delaying disease progression in these women, without causing additional side effects, is heartening. We are planning a Phase 3 pivotal trial which we hope will replicate these positive data."

Participants in the trial were randomized 1:1:1 to receive either (i) nab-paclitaxel plus a daily dose of relacorilant (100 mg), (ii) nab-paclitaxel plus relacorilant (150mg) given "intermittently" (i.e., the day before, the day after, and the day of each weekly nab-paclitaxel infusion) or (iii) nab-paclitaxel alone.

Women who received the higher dose of relacorilant intermittently exhibited a statistically significant improvement in median progression free survival compared to those who received nab-paclitaxel alone (median PFS: 5.6 months versus 3.8 months, hazard ratio: 0.66; p-value: 0.038). Women who received the lower, daily, dose of relacorilant experienced longer progression free survival, but the improvement did not reach statistical significance (5.3 months versus 3.8 months, hazard ratio: 0.83). Full results of the trial, including overall survival, will be available later this year.

"Our trials in other solid tumors continue to progress," added Dr. Grauer. "We expect to have interim data from our RELIANT trial of relacorilant plus nab-paclitaxel in patients with metastatic pancreatic cancer at the end of this quarter. Our trial of relacorilant plus pembrolizumab in patients with adrenal cancer with cortisol excess continues to enroll patients. And by the end of the third quarter, we expect to select an optimal dose of our selective cortisol modulator exicorilant combined with enzalutamide in patients with castration-resistant prostate cancer."

Metabolic Diseases

In Phase 2 trial, patients with presumed NASH administered miricorilant experienced large, rapid reductions in liver fat *
Enrollment continues in GRATITUDE, a 100-patient double-blind, placebo-controlled, Phase 2 trial of miricorilant to reverse recent anti-psychotic-induced weight gain ("AIWG")
Enrollment continues in GRATITUDE II, a 150-patient, double-blind, placebo-controlled Phase 2 trial of miricorilant to reverse long-standing AIWG
"Four of the first five patients who received miricorilant for four weeks in our Phase 2 trial of patients with presumed NASH experienced sharply elevated levels of the liver enzymes ALT and AST, which resolved after miricorilant was withdrawn" said Dr. Grauer. "They also exhibited large reductions in liver fat (see Table 1).

Patient Miricorilant
(per day) Days
on Drug % Liver Fat
at Baseline % Liver Fat
at Follow up Days Between
Last Dose
and Follow-up Relative
Reduction in
% Liver Fat
Patient 1 900 mg 30 17.6 6.1 19 -65.3 %
Patient 2 900 mg 31 27.8 17.1 64 -38.5 %
Patient 3 900 mg 44 28.3 15.0 16 -47.0 %
Patient 4 600 mg 34 12.6 3.3 21 -73.8 %
Table 1: Reduction in liver fat content measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF)
"The improvement in liver fat in these patients was greater and occurred much more rapidly than we had expected. We powered our trial with a planned enrollment of 120 patients to detect a 30 percent reduction in liver fat after twelve weeks’ dosing," said Dr. Grauer. "These results are especially notable given that they were measured many days after miricorilant was stopped. We are gathering more information, consulting with experts in liver disease and formulating our plans to advance miricorilant in NASH."

"In the meantime, our Phase 2 trials evaluating miricorilant as treatment for patients with AIWG – GRATITUDE and GRATITUDE II – continue to add patients," added Dr. Grauer. "We expect to complete enrollment in GRATITUDE II by year-end and GRATITUDE in mid-2022."

Cushing’s Syndrome

Enrollment continues in Phase 3 GRACE trial of relacorilant as a treatment for patients with any etiology of Cushing’s syndrome at sites in the United States, Canada, Europe and Israel; NDA submission expected by second quarter 2023

Enrollment continues in Phase 3 GRADIENT trial of relacorilant as a treatment for patients with Cushing’s syndrome of adrenal origin at sites in the United States, Europe and Israel
"Relacorilant’s Phase 2 efficacy and safety data were extremely promising. We expect GRACE to serve as the basis for our NDA in Cushing’s syndrome. GRACE is accruing patients and generating data and we have observed an improved enrollment rate at our sites in the United States over the last few months. While the pandemic continues to suppress enrollment in GRACE and GRADIENT, particularly in Europe, where the pace of recovery from COVID has lagged, we remain on track for NDA submission by the second quarter of 2023," said Dr. Grauer. "GRADIENT will produce valuable data about the role of cortisol modulation in an etiology of Cushing’s syndrome that has not previously been subject to a rigorous, controlled study."

Conference Call

We will hold a conference call on May 6, 2021, at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time). To participate, Click this link (listen-only mode) or dial 1-888-204-4368 from the United States or 1-313-209-4906 internationally approximately 15 minutes before the start of the call. The passcode will be 8720277. A replay will be available on the Investors / Past Events tab of our website.

Hypercortisolism

Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients diagnosed each year. Symptoms vary, but most patients experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Hypercortisolism can affect every organ system in the body and can be lethal if not treated effectively. Corcept holds patents covering the composition of relacorilant and the use of cortisol modulators, including Korlym, in the treatment of patients with hypercortisolism