On August 12, 2021 Monopar Therapeutics Inc. (Monopar or the Company) (Nasdaq: MNPR), a clinical-stage biopharmaceutical company primarily focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported second quarter 2021 financial results and recent business updates (Press release, Monopar Therapeutics, AUG 12, 2021, View Source [SID1234586463]).

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Recent Business Updates

Validive

Monopar’s Phase 2b/3 VOICE clinical trial of Validive (clonidine HCl mucobuccal tablet) for the prevention of severe oral mucositis (SOM) in patients undergoing chemoradiotherapy (CRT) for oropharyngeal cancer successfully reached its target of 20 activated clinical trial sites for the Phase 2b portion of the trial. Monopar plans to activate additional clinical trial sites, potentially including sites outside of the U.S. There is no FDA-approved prevention or treatment for CRT-induced SOM. The VOICE trial is on track for reaching interim analysis in the first half of 2022.
Camsirubicin and MNPR-202 and Related Analogs

The U.S. Food and Drug Administration cleared Monopar to proceed under its Investigational New Drug (IND) application with an open-label Phase 1b dose-escalation clinical trial evaluating camsirubicin plus growth factor support (pegfilgrastim) in patients with advanced soft tissue sarcoma (ASTS). Monopar anticipates dosing the first patient in the fourth quarter of 2021.
Monopar entered into a collaboration agreement with the Cancer Science Institute of Singapore, one of Asia’s premier cancer research centers, at the National University of Singapore (consistently ranked as one of the world’s top universities) to evaluate the activity of MNPR-202 and related analogs in preclinical models of multiple types of cancer. MNPR-202, a camsirubicin analog, was designed to retain the same potentially non-cardiotoxic backbone as camsirubicin but is modified at other positions which may enable it to be efficacious in certain cancers that are resistant to camsirubicin and doxorubicin. MNPR-202 and related analogs are covered under a newly issued U.S. composition of matter patent (US10,450,340).
MNPR-101 RIT and Related Compounds

Monopar and NorthStar Medical Radioisotopes, LLC (NorthStar) filed a provisional patent application with the U.S. Patent and Trademark Office (USPTO) titled "Bio-Targeted Radiopharmaceutical Compositions Containing Ac-225 and Methods of Preparation." Radiopharmaceutical therapy is a promising approach to treat cancer and other diseases using radioactive metals bound to proteins/antibodies to target and kill cells. Actinium-225 (Ac-225) is emerging as a radioactive isotope of choice for radiopharmaceuticals due to favorable properties such as its long half-life and selective induction of localized tumor cell death.

Monopar and NorthStar filed a provisional composition of matter patent application titled "Urokinase Plasminogen Activator Receptor-Targeted Radiopharmaceutical" covering a radiotherapeutic consisting of Monopar’s proprietary antibody MNPR-101 bound to Ac-225 via the metal binding agent PCTA. This radioimmunotherapeutic (RIT) has demonstrated 98% radiochemical purity and high stability, and has the potential to be a highly selective, potent treatment for a variety of cancers, severe COVID-19, and other diseases characterized by aberrant urokinase plasminogen activator receptor expression.
Additions to Monopar’s Executive Management Team

Monopar appointed Andrew Cittadine, MBA, as its Chief Operating Officer. Mr. Cittadine is an experienced healthcare executive and serial entrepreneur who has founded or led multiple healthcare businesses from concept through acquisition by Fortune Global 1000 firms. These include founding two successful diagnostic imaging companies, Sensant Corp. and American Biooptics, where he also served as CEO, and led both through stock or asset acquisitions by Siemens and Olympus, respectively. He also served as CEO of a critical care company, SonarMed, which was acquired by Medtronic. Mr. Cittadine brings to Monopar considerable leadership experience, including managing manufacturing and quality systems implementation, executing multi-center clinical trials, and achieving regulatory clearances for new technologies in both the U.S. and Europe.

Monopar appointed Octávio Costa, MD, as its Chief Medical Officer. Dr. Costa joined Monopar with over 30 years of experience overseeing clinical development, clinical operations, development strategy and global medical affairs. He has extensive Phase 1 through Phase 4 clinical development expertise and related regulatory experience. Dr. Costa’s previous roles include positions of increasing responsibility in clinical development at Merck, Celgene, Novartis and most recently as Chief Medical Officer at Rafael Pharmaceuticals. He has played an important role in the development and life-cycle management of significant marketed oncology products, including the blockbuster product REVLIMID (lenalidomide) in Latin America.
Results for the Second Quarter Ended June 30, 2021, Compared to the Second Quarter Ended June 30, 2020

Cash and Net Loss

Cash and cash equivalents as of June 30, 2021, were $24.3 million. Monopar anticipates that its current cash and cash equivalents will fund the Company’s major programs at least through September 2022, including: completing the Phase 2b portion of the VOICE clinical trial and commencing of the Phase 3 portion; funding the camsirubicin Phase 1b clinical trial; continuing advancement of the MNPR-101 RIT program including related compounds; continuing the development of MNPR-101 and related technologies in cancer; and developing MNPR-202 and related analogs in various cancers. The Company plans to raise additional funds and/or engage a partner within the next 12 months to complete the VOICE clinical program and continue the camsirubicin clinical development beyond the Phase 1b clinical trial.

Net loss for the second quarter of 2021 was $2.1 million or $0.17 per share compared to net loss of $1.4 million or $0.14 per share for the second quarter of 2020.

Research and Development (R&D) Expenses

R&D expenses for the second quarter of 2021 were $1.4 million compared to $0.8 million for the second quarter of 2020. This increase of $0.6 million was primarily attributed to increases of (1) $0.3 million for VOICE clinical trial expenses, (2) $0.2 million for R&D personnel expenses, and (3) $0.1 million for planning of the Phase 1b camsirubicin clinical trial including regulatory and manufacturing-related expenses.

General and Administrative (G&A) Expenses

G&A expenses for the second quarter of 2021 were $0.6 million, essentially the same as the G&A expenses for the second quarter of 2020.

On August 12, 2021 Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180) and Coherus BioSciences, Inc. ("Coherus", Nasdaq: CHRS) reported that the United States Food and Drug Administration ("FDA") has recently granted Breakthrough Therapy Designation ("BTD") for toripalimab in combination with chemotherapy (gemcitabine and cisplatin) for the 1st line treatment of recurrent or metastatic nasopharyngeal carcinoma ("NPC") (Press release, Coherus Biosciences, AUG 12, 2021, View Source [SID1234586462]). The FDA had earlier granted BTD for toripalimab monotherapy for patients with recurrent or metastatic NPC with disease progression on or after platinum-containing chemotherapy.

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BTD is intended to expedite the development and regulatory review of drugs where preliminary clinical evidence demonstrates substantial improvement over existing therapies for a severe or life-threating disease. Drugs with BTD will be granted closer FDA guidance – including that from senior FDA officials – and various forms of support to avail patients with new therapy as soon as possible.

Junshi Biosciences expects to complete the biologics license application ("BLA") submission for toripalimab plus chemotherapy for 1st line NPC and for toripalimab monotherapy for 2nd or 3rd line NPC later this quarter.

"We are pleased to have received Breakthrough Therapy designation for our novel PD-1 blocking antibody, toripalimab, for nasopharyngeal carcinoma, which is an aggressive cancer with no immuno-oncology treatment options approved in the United States," said Dr. Patricia Keegan, Chief Medical Officer of Junshi Biosciences. "We look forward to working closely with the FDA during the BLA review process and with our partner, Coherus, to bring toripalimab to NPC patients in the U.S., if approved."

The Breakthrough Therapy designation is supported by data from the Phase 3 clinical trial "JUPITER-02" evaluating toripalimab in combination with chemotherapy for the first-line treatment of NPC. In this study, toripalimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression free survival ("PFS") compared to chemotherapy alone (assessed by a blinded independent review committee ("BIRC") per RECIST v1.1). JUPITER-02 also met secondary endpoints of PFS assessed by the investigator and objective response rate assessed by BIRC. There was also a longer duration of response, a higher disease control rate, and higher one- and two-year survival rates for the toripalimab arm. The safety profile of toripalimab is consistent with that observed in previously reported toripalimab clinical trials and the safety profile of this class of drugs. The result of JUPITER-02 was recently presented at the ASCO (Free ASCO Whitepaper) plenary session (#LBA2) and full results can be found in the August 2021 on-line edition of Nature Medicine.

About toripalimab
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 is thought to recharge the immune system’s ability to attack and kill tumor cells.

More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally, including in China and the United States. Pivotal clinical trials are ongoing or completed evaluating the safety and efficacy of toripalimab for a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.

In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). On December 17, 2018, toripalimab was granted a conditional approval from the National Medical Products Administration (NMPA) for the second-line treatment of unresectable or metastatic melanoma. In December 2020, toripalimab was successfully included in the updated National Reimbursement Drug List. In February 2021, the supplemental NDA for toripalimab in combination with chemotherapy for the first-line treatment of patients with advanced, recurrent or metastatic nasopharyngeal carcinoma was accepted by the NMPA. In the same month, the NMPA granted a conditional approval to toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy. In April, NMPA granted a conditional approval to toripalimab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

In the United States, a rolling submission of the first toripalimab Biologics License Application (BLA) is underway for the treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC). The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for toripalimab in combination with chemotherapy for the 1st line treatment of recurrent or metastatic nasopharyngeal carcinoma ("NPC") and also for toripalimab monotherapy in second or third line treatment of recurrent or metastatic NPC. There are currently no PD-1 blocking antibodies indicated for use in NPC in the United States. Additionally, FDA has granted Fast Track status for the development of toripalimab for the treatment of mucosal melanoma and orphan drug designation for NPC, mucosal melanoma and soft tissue sarcoma. Earlier in 2021 Coherus in-licensed rights to develop and commercialize toripalimab in the United States and Canada. Coherus and Junshi Biosciences plan to file additional toripalimab BLAs with the FDA over the next three years for multiple rare cancers and highly prevalent cancers.

On August 12, 2021 Nimbus Therapeutics, a biotechnology company designing breakthrough medicines through structure-based drug discovery and development, reported the extension of its collaboration with Schrödinger, Inc. to discover and design small molecule therapeutics for a number of high-value targets using cutting-edge structure-based drug design approaches (Press release, Nimbus Therapeutics, AUG 12, 2021, View Source [SID1234586461]).

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The agreement extends the collaboration between the two companies, which began in 2009, to advance the usage of computational methods in drug discovery. Since then, the collaboration has generated numerous promising therapeutic candidates, including small molecule inhibitors of acetyl–CoA carboxylase (ACC) and tyrosine kinase 2 (TYK2), which are now in the clinic, and a hematopoietic protein kinase 1 (MAP4K1/HPK1) inhibitor, which Nimbus plans to advance to the clinic later this year.

"Nimbus’ collaboration with Schrödinger over the past 12 years has been groundbreaking, deploying computational horsepower at an unprecedented scale in the industry," said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. "Schrödinger’s deep computational capabilities, paired with Nimbus’ demonstrated expertise in structural biology, small molecule drug discovery and clinical development, provides fertile ground for designing breakthrough medicines over the next decade."

"We are very pleased to embark on this new chapter of Schrödinger’s collaboration with Nimbus and to further expand the frontiers of combining physics-based drug discovery with machine learning," said Ramy Farid, Ph.D., Chief Executive Officer at Schrödinger. "Our collaborative track record underscores the potential of our combined multidisciplinary drug discovery team to design medicines that could provide meaningful benefits for patients."

On August 12, 2021 Kintara Therapeutics, Inc. (Nasdaq: KTRA), a biopharmaceutical company developing novel cancer therapies for patients who are failing or are resistant to current treatment regimens, reported that its Chief Executive Officer, Saiid Zarrabian, will present at the Investor Summit Conference being held August 17 – 18, 2021 (Press release, Kintara Therapeutics, AUG 12, 2021, View Source [SID1234586459]).

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Mr. Zarrabian will deliver his corporate presentation on August 17, 2021 at 12:30 p.m.ET.

Investors can also request a one-on-one meeting with Mr. Zarrabian to be arranged following the conclusion of the conference.

Investors can register here: Q3 Investor Summit Investor Registration

On August 12, 2021 Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing therapies for the treatment of refractive and retinal eye disorders, reported financial results for the second quarter of 2021 and provided a corporate update (Press release, Ocuphire Pharma, AUG 12, 2021, View Source [SID1234586458]).

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"The second quarter of 2021 proved to be highly productive for Ocuphire, with continued success in clinical trials, key pivotal data presentations featured at major medical meetings across both Nyxol and APX3330, and additional IP protection granted for our lead drug candidate Nyxol," said Mina Sooch, MBA, President and CEO of Ocuphire Pharma.

"Following our first quarter announcement of positive MIRA-2 Phase 3 results of Nyxol for the treatment of reversal of mydriasis (RM), we also announced positive top-line results from our VEGA-1 Phase 2 study, which evaluated Nyxol in combination with low-dose pilocarpine (LDP) for the treatment of presbyopia, the gradual loss of your eyes’ ability to focus on nearby objects. In our view, RM and presbyopia both represent attractive and large US and global market opportunities, with each indication having a significant unmet medical need with very few if any pharmaceutical treatment options. Following the recent ASCRS meeting, it is also clear that global pharmaceutical and consumer healthcare companies are aggressively pursuing innovative new medicines, further validating the significant commercial potential for the large presbyopia market. Based upon the success of our VEGA-1 trial, we are highly confident that Nyxol in combination with LDP presents a potentially best-in-class therapeutic solution that can address the needs of the presbyopia patient population."

"With our balance sheet recently strengthened in the second quarter combined with our capital efficient operations, Ocuphire is well positioned to deliver additional late-stage clinical milestones in 2022 for Nyxol and APX3330 while continuing our global business development efforts."

Key Anticipated Future Milestones

Reversal of Mydriasis (RM): Initiate second Phase 3 (MIRA-3) registration trial and a small pediatric trial (MIRA-4) in the second half of 2021 investigating Nyxol with results expected in early 2022; Planning to file NDA submission with FDA for Nyxol in RM indication in late 2022
Presbyopia: Initiate Phase 3 program (VEGA-2/3) in first half of 2022 investigating Nyxol and LDP
Night Vision Disturbances: Completion of enrollment expected by year-end 2021 and top-line data expected in early 2022 from Phase 3 (LYNX-1) registration trial investigating Nyxol
Diabetic Retinopathy and Diabetic Macular Edema: Completion of enrollment in Phase 2 (ZETA-1) trial investigating APX3330 and top-line data expected in 2022

Second Quarter and Recent Business Highlights

Clinical Development

In June, the Company announced successful results from the VEGA-1 Phase 2 trial of Nyxol plus low-dose pilocarpine (LDP) for the treatment of presbyopia; the trial met its primary endpoint of 3 lines of near vision improvement and multiple key secondary endpoints such as fast onset of action and durability with statistical significance and a favorable safety profile (including no headaches)
In April, the Company initiated the ZETA-1 Phase 2 clinical trial to evaluate oral APX3330 in non-proliferative diabetic retinopathy (NPDR) and mild proliferative diabetic retinopathy (mild PDR)

Presentations and Publications

In July, the Company announced publication in the Journal of Cellular Signaling featuring Ocuphire’s novel oral Ref-1 inhibitor APX3330 in Phase 2 trial for the treatment of retinal disease which highlighted the favorable safety profile of APX3330 and its unique anti-angiogenic and anti-inflammatory mechanism of action properties relevant to a broad range of retinal diseases
In July at the 2021 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting, Dr. Jay S. Pepose, Medical Advisor and Board Director, presented two papers featuring the positive results Phase 2 Presbyopia (VEGA-1) and Phase 3 Reversal of Mydriasis (MIRA-2)
In July, Mina Sooch, CEO, participated in the presbyopia drug therapy panel at the Eyecelerator held on July 22nd and in the Eye on Innovation panel at the Virtual Salon Series held on July 28th
In late May, Ocuphire hosted a Key Opinion Leader Event on Nyxol as a potential new treatment option for reversing pharmacologically induced mydriasis, highlighting recent positive Phase 3 results from the MIRA-2 Phase 3 registrational study
In May at the 2021 Association for Research in Vision and Ophthalmology (ARVO) Virtual Annual Meeting, Ocuphire presented data for APX3330 on pre-clinical ocular data and predictive human retina and plasma model data

Corporate

Announced closing of a $15 million registered direct offering and just over $4 million from ATM, extending cash runway into late 2022
Appointed Jay S. Pepose, M.D., Ph.D. to the Company’s Board of Directors
Received two new U.S. patent grants covering Nyxol including Nyxol plus LDP claims for the treatment of presbyopia through 2039
Entered into a license agreement granting Processa Pharmaceuticals (Nasdaq: PCSA) an exclusive license to develop, manufacture and commercialize globally RX-3117 (Rexahn legacy oncology intellectual property), excluding China, Hong Kong, Macau, Republic of Singapore and Taiwan (already licensed to BioSense Global LLC ("BioSense"))
Ocuphire (Nasdaq: OCUP) added to the Russell Microcap Index

Second Quarter and Year to Date 2021 Financial Highlights

As of June 30, 2021, the Company had cash and cash equivalents of approximately $24.2 million. Net cash used in operating activities for the three and six months ended June 30, 2021, was $4.3 million and $10.1 million, respectively.

Collaborations revenue was $0.1 million for the three and six months ended June 30, 2021. Revenue during the periods was derived from the license agreement with BioSense related to certain technology transfers. There was no collaborations revenue recognized during the comparable prior year periods.

General and administrative expenses for the three and six months ended June 30, 2021, were $3.4 million and $5.1 million, respectively, compared to $0.6 million and $0.9 million, respectively, for the three and six months ended June 30, 2020. The increases from the comparable periods in 2020 were attributable to increased costs primarily in administrative employee headcount, stock-based compensation, insurance, legal and settlement costs, and costs associated with operating as a public company subsequent to the reverse merger.

Research and development expenses for the three and six months ended June 30, 2021, were $3.8 million and $7.3 million, respectively, compared to $0.7 million and $0.9 million, respectively, for the three and six months ended June 30, 2020. The increases from the comparable periods in 2020 were primarily attributable to four new clinical trials and manufacturing activities for Nyxol and APX3330 as well as regulatory, preclinical, and other development activities.

There were no acquired in-process research and development expenses in the current six-month period. In the prior year in connection with the sublicense agreement with Apexian for the continued research, development and potential commercialization of APX3330, the Company recorded acquired in-process research and development expenses of $2.1 million during the six-month period ended June 30, 2020.

The total loss from operations for the three and six months ended June 30, 2021 was $7.1 million and $12.3 million, respectively, compared to $1.3 million and $4.0 million for the three and six months ended June 30, 2020, respectively. This included non-cash stock-based compensation expense of $0.5 million and $1.0 million during the three and six months ended June 30, 2021, respectively, and $0.3 million and $0.4 million during the three and six months ended June 30, 2020, respectively.

For further details on Ocuphire’s financial results, including results for the three and six month periods ended June 30, 2021 refer to the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2021, to be filed with the Securities and Exchange Commission.