On August 16, 2021 Gracell Biotechnologies Inc. (NASDAQ: GRCL) ("Gracell"), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported an exclusive license agreement with FutureGen Biopharm ("FutureGen"), an innovative biopharmaceutical company, to develop engineered immune cell therapies targeting Claudin 18.2 ("CLDN18.2") in solid tumors (Press release, Gracell Biotechnologies, AUG 16, 2021, View Source [SID1234586657]).

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The collaboration aims to leverage Gracell’s extensive experience in immune cell therapy in synergy with FutureGen’s fully human CLDN18.2 antibodies to develop, manufacture and commercialize novel immune cell therapies for the treatment of patients with CLDN18.2 positive cancers.

CLDN18.2 is a tumor-specific marker that is overexpressed in a variety of tumor tissues, including in gastric or gastroesophageal junction cancers, pancreatic cancers and esophageal cancers, but rarely expressed in normal human tissues. This feature supports the therapeutic potential of CLDN18.2 as a key target for immune cell therapies. In particular, gastric cancer (around 70%[1] CLDN18.2 expression) is among the most frequently diagnosed malignancies worldwide and the second leading cause of cancer-related death. An estimated 1,033,701 new cases and 782,685 deaths occurred in 2018[2], representing a highly unmet medical need in treating gastric cancer.

"Gracell has been making significant progress in developing innovative CAR-T therapies for solid tumors as well as hematological malignancies," Dr. William (Wei) Cao, Founder, Chairman and Chief Executive Officer of Gracell said. "This partnership with FutureGen marks another key milestone in our persistent efforts for treating solid tumors. Moving forward, we expect to explore more strategic alliances to identify additional targets that maximize the value of our highly differentiated technology platforms and eventually benefit cancer patients worldwide."

"Gracell has been optimizing its proprietary Enhanced CAR technology to improve CAR-T cell persistence and efficacy in solid tumors. The preliminary clinical investigator-initiated trial data of our first generation Enhanced CAR-T for solid tumors has shown tolerability and preliminary efficacy. These initial results have been accepted to be published soon in Cellular & Molecular Immunology," said Dr. Lianjun Shen, Senior Vice President, Head of Research and Development at Gracell. "We are very excited to partner with FutureGen to develop next generation immune cell therapies against CLDN18.2-expressing malignancies, and hope to unlock significant potential of our next generation Enhanced CAR-T therapies for solid tumors, one of our founding missions."

Dr. Zhaoyu Jin, the Founder and Chief Executive Officer of FutureGen said, "The specific CLDN18.2 antibody has been developed through our innovative STEP and CAP technology platforms. The fine-tuned affinity of antibody for CAR-T application may eliminate CLDN18.2 positive tumor cells more specifically with better safety profile. We are very excited to collaborate with Gracell, a lead company in the cell and gene therapy industry, to leverage their innovative Enhanced CAR-T technology platform and experience in the field and our proprietary cutting-edge technologies to develop advanced treatments across solid tumors."

Under the terms of the agreement, FutureGen will receive an upfront payment and will be eligible to receive additional payments based on the achievement of non-clinical validation, clinical development and commercialization milestones, as well as low single-digit royalties.

About CLDN18.2

CLDN18.2, a small transmembrane protein with four transmembrane domains and two extracellular loops, is overexpressed in a significant proportion of gastric cancers and esophageal adenocarcinomas. The restricted expression makes it a promising target for the treatment of gastric or gastroesophageal junction cancers, pancreatic cancers, etc. Overall, CLDN18.2 is prevalently expressed in the cancer tissues of approximately 70% of gastric cancer patients and approximately 60% of pancreatic cancer patients. CLDN18.2-specific antibodies developed to target CLDN18.2 have exhibited anti-tumor activity in preclinical studies.[3]

About Enhanced CAR

Enhanced CAR is Gracell’s proprietary technology that further strengthens the functionality of CAR-T cells, for example by overcoming the immunosuppressive tumor micro-environment (TME) and/or increasing cytokine signaling. Gracell utilizes gene editing technologies to edit some check point inhibitor(s) or/and cytokine(s) or cytokine receptor(s) on CAR-T cells to release potential suppression from tumor cells and other suppressive immune cells in tumor tissue to enhance CAR-T cells’ functionality. Our second generation Enhanced CAR technology can be implemented to many other targets in several types of solid tumors.

On August 16, 2021 Novo Nordisk reported that it initiated a share repurchase programme in accordance with Article 5 of Regulation No 596/2014 of the European Parliament and Council of 16 April 2014 (MAR) and the Commission Delegated Regulation (EU) 2016/1052 of 8 March 2016 (the "Safe Harbour Rules") (Press release, Novo Nordisk, AUG 16, 2021, View Source [SID1234586625]). This programme is part of the overall share repurchase programme of up to DKK 18 billion to be executed during a 12-month period beginning 3 February 2021.

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Under the programme initiated 4 August 2021, Novo Nordisk will repurchase B shares for an amount up to DKK 3.3 billion in the period from 5 August 2021 to 1 November 2021.

Since the announcement of the programme, the following transactions have been made:

The details for each transaction made under the share repurchase programme are published on novonordisk.com.

Transactions related to Novo Nordisk’s incentive programmes have resulted in a net transfer from Novo Nordisk of 32,026 B shares in the period from 5 August 2021 to 13 August 2021. The shares in these transactions were not part of the Safe Harbour repurchase programme.

With the transactions stated above, Novo Nordisk owns a total of 18,096,886 B shares of DKK 0.20 as treasury shares, corresponding to 0.8% of the share capital. The total amount of A and B shares in the company is 2,310,000,000 including treasury shares.

Novo Nordisk expects to repurchase B shares for an amount up to DKK 18 billion during a 12- month period beginning 3 February 2021. As of 13 August 2021, Novo Nordisk has since 3 February 2021 repurchased a total of 19,290,414 B shares at an average share price of DKK 479.66 per B share equal to a transaction value of DKK 9,252,771,246.

On August 16, 2021 Protalix BioTherapeutics, Inc. (NYSE American: PLX) (TASE: PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported financial results for the second quarter ended June 30, 2021 and provided a financial and business update (Press release, Protalix, AUG 16, 2021, View Source [SID1234586642]).

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"We continue to work closely with the FDA to address the issues raised in the Complete Response Letter received in April for PRX-102 for the proposed treatment of adult patients with Fabry disease," said Dror Bashan, Protalix’s President and Chief Executive Officer. "We look forward to the meeting with the FDA, which has been scheduled for September 9, 2021. In addition, we strengthened our balance sheet by entering into definitive agreements with a majority of our institutional note holders relating to exchanges by such note holders of a total of $54.65 million principal amount of our outstanding 7.50% Senior Secured Convertible Notes due 2021 for an aggregate of $28.75 million principal amount of newly issued 7.50% Senior Secured Convertible Notes due 2024, $25.90 million in cash and accrued and unpaid interest through the closing date. We plan to close the exchanges as soon as practicable. This transaction will allow us the use of our cash resources to continue to realize the PRX-102 potential and advance our early-stage pipeline. We are grateful for the continued support from our team members and external partners and look forward to a productive finish to 2021."

2021 Second Quarter and Recent Business Update

Regulatory Updates

On April 28, 2021, the Company, together with its development and commercialization partner, Chiesi Farmaceutici S.p.A., or Chiesi, announced the receipt of a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the Biologics License Application (BLA) seeking accelerated approval of pegunigalsidase alfa, or PRX-102, for the proposed treatment of adult patients with Fabry disease. The CRL did not report any concerns relating to the potential safety or efficacy of PRX-102 in the submitted data package.
On August 2, 2021, the Company announced that a Type A meeting request was submitted to the FDA to discuss the CRL dated April 27, 2021 regarding the BLA for PRX-102 for the proposed treatment of adult patients with Fabry disease. The FDA has scheduled the Type A meeting for September 9, 2021.
Clinical Advancements

On June 2, 2021, the Company, together with Chiesi, announced initial top-line results from an interim analysis of the phase III BALANCE clinical trial, a study designed to evaluate the safety and efficacy of 1 mg/kg of PRX-102 dosed every two weeks compared to agalsidase beta (Fabrazyme).
Based on the interim analysis of the 12-month data generated from the BALANCE study, and in combination with previously reported positive data from the phase III BRIGHT and BRIDGE clinical trials of PRX-102, Protalix and Chiesi intend to submit a Marketing Authorization Application (MAA) to the European Medicines Agency for the review of PRX-102 for the proposed treatment of Fabry disease, subject to a positive meeting with the EMA rapporteur.
Corporate & Financial Developments

On August 12, 2021, the Company entered into definitive agreements relating to exchanges of an aggregate of $54.65 million principal amount of the Company’s outstanding 7.50% Senior Secured Convertible Notes due 2021 for an aggregate of $28.75 million principal amount of newly issued 7.50% Senior Secured Convertible Notes due 2024 (the "Exchange Notes"), $25.90 million in cash and accrued and unpaid interest through the closing date. The exchanges are expected to close as soon as practicable, subject to satisfaction of certain closing conditions. At closing, we will have reduced our debt by $28.75 million and effectively extended the maturity for substantially all of the remaining debt from 2021 until 2024. The support and willingness of our note holders to extend the maturity underscores their confidence in our core technology and expanding pipeline.
On May 13, 2021, the Company and Chiesi entered into a binding term sheet pursuant to which they amended the two exclusive license and supply agreements for PRX-102 in order to provide the Company with near-term capital. Chiesi agreed to make a $10.0 million payment to the Company before the end of the second quarter in exchange for a $25.0 million reduction in a longer-term regulatory milestone payment in the Ex-U.S. Exclusive License and Supply Agreement. All other regulatory and commercial milestone payments remain unchanged. The Company and Chiesi also agreed to negotiate certain manufacturing related matters. The $10.0 million payment was received in June 2021.
On July 2, 2021, the Company entered into an ATM Sales Agreement with H.C. Wainwright & Co., LLC (the agent) whereby the Company may sell, from time-to-time, shares of its common stock through the agent up to an aggregate offering price of $20.0 million. Upon execution of the sales agreement, the Company terminated the ATM Equity Offering Sales Agreement it had previously entered into with BofA Securities, Inc.
Second Quarter 2021 Financial Highlights

The Company recorded revenues from selling goods of $3.2 million during the three months ended June 30, 2021, a decrease of $0.4 million, or 11%, compared to revenues of $3.6 million for the same period of 2020.
Revenues from license and R&D services for the three months ended June 30, 2021 were $3.2 million, a decrease of $4.1 million, or 56%, compared to $7.3 million for the same period of 2020. Revenues from license and R&D services are comprised primarily of revenues the Company recognized in connection with its license and supply agreements with Chiesi. The decrease resulted primarily from an updated costs estimation throughout the trials until completion in the amount of $4.1 million and from revenues recognized in connection with the progress of the Company’s clinical trials that have been completed during 2020.
Cost of goods sold for the three months ended June 30, 2021 was $4.7 million, an increase of $2.9 million, or 161%, compared to $1.8 million for the same period in 2020. The increase in cost of goods sold was primarily the result of certain one-time manufacturing costs incurred while preparing for the then anticipated FDA approval of the PRX-102 BLA.
Research and development expenses for the three months ended June 30, 2021 were $7.7 million, a decrease of $1.5 million, or 16%, compared to $9.2 million for the same period of 2020. The decrease was primarily the result of the completion of two out of the three phase III clinical trials of PRX-102 and reduced costs related to the BALANCE study. The Company expects research and development expenses to continue to be its primary expense as it enters into more advanced stages of preclinical and clinical trials for certain of its product candidates.
Selling, general and administrative expenses for the three months ended June 30, 2021 were $3.2 million, an increase of $1.0 million, or 45%, compared to $2.2 million for the same period in 2020. The increase resulted primarily from an increase in corporate costs related to insurance and funding.
Financial expenses, net were $2.1 million for the three months ended June 30, 2021 and $1.9 million for the three months ended June 30, 2020. The increase resulted primarily from an increase in the amortization of debt issuance costs and debt discount.
Cash, cash equivalents and short-term bank deposits were approximately $76.9 million at June 30, 2021.
Net loss for the three months ended June 30, 2021 was approximately $11.2 million, or $0.25 per share, basic and diluted, compared to a net loss of $4.2 million, or $0.13 per share, basic and diluted, for the same period in 2020.
Conference Call and Webcast Information

The Company will host a conference call today, August 16, 2021 at 8:30 am Eastern Daylight Time, to review the clinical, corporate, and financial highlights, which will also be available by webcast. To participate in the conference call, please dial the following numbers prior to the start of the call:

Conference Call Details:

The conference call will be webcast live from the Company’s website and will be available via the following links:

Webcast Details:

Company Link: View Source

Webcast Link: View Source

Please access the websites at least 15 minutes ahead of the conference to register, download and install any necessary audio software.

The conference call will be available for replay for two weeks on the Events Calendar of the Investors section of the Company’s website, at the above link.

On August 16, 2021 ESSA Pharma Inc. ("ESSA" or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported financial results for the fiscal third quarter ended June 30, 2021 (Press release, ESSA, AUG 16, 2021, View Source [SID1234586658]). All references to "$" in this release refer to United States dollars, unless otherwise indicated.

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"During this quarter, the Company continued to focus on the execution of the Phase 1a clinical program of EPI-7386 as a monotherapy in patients with late-stage metastatic castration-resistant prostate cancer ("mCRPC") whose tumors have progressed on multiple current standard-of-care therapies, including antiandrogens," said Dr. David R. Parkinson, M.D., President and Chief Executive Officer of ESSA Pharma Inc. "In this heavily pretreated cohort of patients, EPI-7386 continues to be safe, well-tolerated, with generally good drug exposures, and adverse-events typical of those associated with antiandrogen therapy. Patients are currently being dosed at 600 mg, 800 mg, and 1,000 mg QD, with each of these dose levels being cleared as safe and tolerable. Given the favorable tolerability of the drug and the wide therapeutic window seen in preclinical studies, we plan to enroll additional higher dose cohorts using a twice daily (BID) dosing schedule to further enhance patient drug exposures. In addition, we are planning to file a protocol amendment to focus further monotherapy development in less heavily pretreated patients in whom we believe the androgen receptor pathway continues to be the primary driver of tumor growth. Our goal is to establish a recommended Phase 2 dose ("RP2D") for monotherapy during the first half of 2022 and commence the expansion Phase 1b study soon thereafter in earlier, less heavily pretreated and more biologically characterized patients. We look forward to presenting a clinical readout of the Phase 1a monotherapy trial in the first half of 2022."

Dr. Parkinson continued, "In parallel, our development of EPI-7386 in combination with current antiandrogens in mCRPC patients remains on track. The ESSA-managed clinical trial collaboration with Astellas (enzalutamide) will begin in the fourth quarter of 2021. The EPI-7386 combination studies with other antiandrogens that were announced earlier this year are on track and are anticipated to begin in late 2021 or early 2022. Lastly, using nuclear magnetic resonance studies, we have achieved our long-term preclinical goal of demonstrating definitive evidence that EPI-7386 binds to the N-terminal domain of the androgen receptor and look forward to presenting these results at an upcoming scientific conference this year. As a result of the successful financing earlier this year, our cash and short-term investments of over $202 million provide us a cash runway into 2024 and fully fund the current development programs."

Recent Clinical and Corporate Highlights

On April 28, 2021, the Company announced a clinical collaboration with Bayer to evaluate EPI-7386 in combination with Bayer’s androgen receptor inhibitor darolutamide in patients with metastatic castration-resistant prostate cancer ("mCRPC"). Under the terms of the agreement, Bayer may sponsor and conduct a Phase 1/2 study to evaluate the safety, pharmacokinetics and efficacy of the combination of EPI-7386 and darolutamide in mCRPC patients. ESSA will supply EPI-7386 for the trial and will retain all rights to EPI-7386.

On April 10, 2021, the Company reported new preclinical data on EPI-7386 at the 2021 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that in vitro EPI-7386 can prevent the androgen receptor from binding to genomic DNA and can inhibit AR related transcription in prostate cancer cell lines expressing androgen receptor ("AR") splice variants including the AR-v567es variant. The results also demonstrate that combining EPI-7386 with enzalutamide in vitro results in a broader and deeper inhibition of the AR pathway.
Summary Financial Results

Net Loss. ESSA recorded a net loss of $8.8 million ($0.21 loss per common share based on 41,018,024 weighted average common shares outstanding) for the quarter ended June 30, 2021, compared to a net loss of $4.9 million ($0.24 loss per common share based on 20,824,568 weighted average common shares outstanding) for the quarter ended June 30, 2020. For the period ended June 30, 2021, this included non-cash share-based payments of $2.8 million compared to $1.5 million for the prior year, recognized for stock options granted and vesting.

Research and Development ("R&D") expenditures. R&D expenditures for the quarter ended June 30, 2021 were $6.2 million compared to $2.7 million for the quarter ended June 30, 2020 and includes non-cash costs related to share-based payments ($1.2 million for period ended June 30, 2021 compared to $382,941 for period ended June 30, 2020). The increase in R&D expenditures for the third quarter were primarily related to preclinical research with work directed to the completion of the IND filing in March 2020 and chemistry and manufacturing costs in preparation for the Phase 1 study.

General and administration ("G&A") expenditures. G&A expenditures for the quarter ended June 30, 2021 were $3.1 million compared to $2.2 million for the quarter ended June 30, 2020 and include non-cash costs related to share-based payments of $1.5 million for the period ended June 30, 2021 compared to $1.1 million for the period ended June 30, 2020. The increase in the third quarter is the result of increased share-based payments related to the expense recognized in relation to the grant and vesting of these equity instruments.
Liquidity and Outstanding Share Capital

At June 30, 2021, the Company had available cash reserves and short-term investments of $202,263,003 reflecting the gross proceeds of the February 2021 financing of $150.0 million and July 2020 financing of $48.9 million, less operating expenses in the intervening period.

As of June 30, 2021, the Company had 41,854,916 common shares issued and outstanding.

In addition, as of June 30, 2021 there were 5,359,750 common shares issuable upon the exercise of warrants and broker warrants. This includes 5,045,000 prefunded warrants at an exercise price of $0.0001, and 314,750 warrants at a weighted average exercise price of $49.69. There are 6,803,230 common shares issuable upon the exercise of outstanding stock options at a weighted-average exercise price of $5.20 per common share.

About EPI-7386
EPI-7386 is an investigational, highly-selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor. EPI-7386 is currently being studied in a Phase 1 clinical trial (NCT04421222) in men with mCRPC whose tumors have progressed on current standard-of-care therapies. The Phase I clinical trial of EPI-7386 began in calendar Q3 of 2020 following FDA allowance of our Investigational New Drug application and Health Canada acceptance. The U.S. FDA has granted Fast Track designation to EPI-7386 for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA retains all rights to EPI-7386 worldwide.

On August 16, 2021 Cytocom, Inc. (NASDAQ: CBLI), a leading biopharmaceutical company creating next-generation immune therapies that focus on immune restoration and homeostasis, reported that the audio archive of the second quarter 2021 corporate and financial results conference call may be accessed from the "Investors" section of the Cytocom website at https://www.cytocom.com/investors/ (Press release, Cytocom, AUG 16, 2021, https://www.cytocom.com/2021/08/16/cytocom-inc-second-quarter-2021-financial-results-conference-call-replay-available-via-webcast/?utm_source=rss&utm_medium=rss&utm_campaign=cytocom-inc-second-quarter-2021-financial-results-conference-call-replay-available-via-webcast [SID1234586626]). The replay of the webcast will be archived on the website for 90 days beginning at approximately 10:00 a.m. ET, on August 16, 2021.

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