On February 14, 2023 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported the following update on its currently enrolling open-label Phase 1b camsirubicin Maximum Tolerated Dose (MTD) trial in patients with advanced soft tissue sarcoma (ASTS) (Press release, Monopar Therapeutics, FEB 14, 2023, View Source [SID1234627189]).

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Monopar has opened enrollment for the fifth dose level cohort, at an increased dose of 650 mg/m2, which is nearly 2.5x the highest dose evaluated in any prior camsirubicin clinical trial.
To date, no drug-related cardiotoxicity has been observed with camsirubicin treatment as evaluated by the industry standard left-ventricular ejection fraction (LVEF). This compares favorably to the well-documented dose-restricting cardiotoxicity experienced with doxorubicin treatment, the current first-line treatment for ASTS.
Only 17% of camsirubicin patients in the trial have experienced low grade hair loss; another 8% have experienced >50% hair loss. This compares favorably to the approximately 50% of doxorubicin treated patients in recent ASTS clinical trials reporting some amount of hair loss, with the majority of these patients experiencing >50% hair loss.
Only 8% of camsirubicin patients in the trial have experienced low grade mild oral mucositis. This compares favorably to the roughly 35-40% of doxorubicin treated patients in recent ASTS clinical trials that experienced mild-to-severe oral mucositis.
In addition to the initial Sarcoma Oncology Research Center clinical trial site in Santa Monica, CA, Monopar recently welcomed a second clinical trial site with Dr. Lee Cranmer and the Sarcoma Clinic at the Fred Hutchinson Cancer Center/University of Washington in Seattle, WA.
"We are thrilled to partner with Monopar in exploring camsirubicin in patients facing ASTS. So far, camsirubicin has demonstrated a favorable safety profile at up to the 520 mg/m2 dose level assessed to date," said Dr. Cranmer. "Further escalation of camsirubicin dosing will allow us to confirm its favorable safety profile and explore preliminary evidence of camsirubicin’s clinical activity in advanced sarcoma patients. While only randomized trials will be able to confirm superiority of camsirubicin over doxorubicin, camsirubicin provides hope that we may finally be able to supersede doxorubicin, a drug in use since its approval in 1974, despite its serious drawbacks. Monopar’s continuing efforts to improve ASTS therapy also demonstrate their commitment to changing the treatment landscape for ASTS patients, a population with well-recognized and serious unmet need."

Further information about this actively enrolling, open-label, dose-escalation Phase 1b clinical trial is available at www.ClinicalTrials.gov under study identifier NCT 05043649.

About Camsirubicin

Camsirubicin is a novel, proprietary analog of the widely used cancer drug doxorubicin. It has been previously investigated in ASTS patients in a Phase 1 and a single-arm Phase 2 clinical trial. In these studies, no camsirubicin-treated patients developed the irreversible cardiotoxicity common to doxorubicin at higher cumulative doses. The most frequent adverse event observed in the Phase 1 study was neutropenia, which was mitigated in the Phase 2 study using prophylactic G-CSF. Based on encouraging clinical results from prior clinical trials, the current Phase 1b trial is designed to test camsirubicin at progressively higher doses than previously administered while using concomitant prophylactic G-CSF to prevent neutropenia.

About Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are a diverse type of cancer that typically develop in the connective tissue of the body. According to the American Cancer Society, in 2021, an estimated 13,460 new STS cases were diagnosed in the U.S. alone, with about 5,350 dying from their disease. These tend to be the advanced cases; those with sarcomas that are unresectable and/or have metastasized. The average life expectancy from time of diagnosis for those patients with advanced disease (ASTS) is about 12 to 15 months. Doxorubicin is the current standard of care in the 1st-line setting for ASTS, and has been for decades, since there have been no 1st-line therapeutic advancements that have improved overall survival for this patient population.

On February 14, 2023 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported monotherapy Phase I dose escalation results of the ongoing Phase I/II trial of BT8009, a novel BTC targeting Nectin-4 (Press release, Bicycle Therapeutics, FEB 14, 2023, View Source [SID1234627184]). The results will be presented at the 2023 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium on Friday, February 17, 2023 in San Francisco, California. Today at 8:00 a.m. ET, the Company will host a conference call with BT8009 investigator Dr. Capucine Baldini and Dr. Daniel Petrylak to discuss the data being presented.

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"We are encouraged by the Phase I dose escalation results as they continue to demonstrate the potential for BT8009 to be best-in-class for the treatment of urothelial cancer based on the observed anti-tumor activity and tolerability profile as well as the potential to treat other tumor types with significant unmet need," said Kevin Lee, Ph.D., Chief Executive Officer. "Previously, we had reported a confirmed partial response in a non-small cell lung cancer patient and today we are pleased to announce a confirmed partial response in a breast cancer patient. Both of these patients are Nectin-4 positive. We are continuing to move forward with the dose expansion and Phase II portion of the clinical trial and look forward to providing an update by the end of 2023."

"These data reaffirm the possibility for BT8009 to become a significant new treatment option for patients," said Capucine Baldini, M.D., Medical Oncologist, Gustave Roussy. "The anti-tumor activity observed to date in heavily pre-treated urothelial, lung and breast cancer patients shows that BT8009’s Nectin-4-targeting properties make it a potentially differentiated treatment option compared to other available treatments."

"BT8009 has the potential to become an important player in the treatment landscape for urothelial cancer and other solid tumors," said Daniel Petrylak, M.D., Professor of Medicine and Urology, Yale University. "Clinicians need differentiated treatments for patients that can offer lower rates of rash and neuropathy thus leading to longer durations of treatment. Given the preliminary tolerability and response pattern with BT8009 in this Phase I dose escalation, it justifies exploring BT8009 both as a monotherapy and in combination in the ongoing expansion cohorts."

BT8009, a BTC targeting Nectin-4, has demonstrated anti-tumor activity in heavily pre-treated urothelial, lung and breast cancer patients with signs of differentiation compared to antibody-based approaches. Bicycle established two recommended Phase II doses (RP2Ds) at 5 mg/m2 weekly and 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle). The company is currently focusing its efforts on the 5 mg/m2 weekly dose and enrollment in the expansion cohorts remains ongoing.

Preliminary signs of anti-tumor activity observed. As of the September 20, 2022 data cut off, 49 patients were dosed in the Phase I escalation portion of the ongoing Phase I/II trial with a median of three prior lines of therapy.
A total of 24 urothelial cancer patients were dosed. Of these, eight patients were dosed at the RP2D of 5 mg/m2 weekly.
Among these eight patients, one patient had a complete response (13%), and three patients had a partial response (38%) under the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, resulting in an ITT ORR of 50%. Two additional patients had stable disease for over 16 weeks, resulting in a clinical benefit rate (CBR) of 75%. The remaining two patients in the cohort consisted of one stable disease and one non-evaluable patient.
Of the eight urothelial patients dosed at 5 mg/m2 weekly, seven were response evaluable. Amongst these seven patients, all (100%) were observed to have at least some degree of tumor shrinkage, including the four with a RECIST version 1.1 response (57% ORR on a response-evaluable basis).
As of January 2023, mDOR is estimated to be approximately 14 months. Two out of four responders in this cohort remain on therapy with ongoing responses.
Response rates in urothelial patients in the 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle) and 10 mg/m2 every other week cohort were consistent with that of the 5 mg/m2 weekly cohort on an ITT basis. One of two patients in the 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle) cohort had a partial response and two of four patients in the 10 mg/m2 every other week cohort had a partial response, for an ORR of 50% in each of these cohorts. Both of these cohorts deliver the same amount of MMAE payload as the 5 mg/m2 weekly dose over a six-week period.
Confirmed RECIST response in an NSCLC patient. A confirmed partial response was observed in a 76-year-old patient with Nectin-4 positive metastatic adenocarcinoma. The patient entered the 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle) cohort after four prior lines of therapy, including a checkpoint inhibitor. As of the September 20, 2022 data cutoff, the patient remains on therapy with an ongoing response.
Confirmed RECIST response in a breast cancer patient. A confirmed partial response was observed in a 79-year-old patient with Nectin-4 positive metastatic adenocarcinoma. The patient entered the 10 mg/m2 every other week cohort after one prior line of therapy. As of December 2022, the patient remains on therapy with an ongoing response.
BT8009 was well tolerated across all 49 patients in the study, with a low incidence of adverse events common to antibody-based approaches. The most common treatment-related adverse events across the study were gastroenterologically related and fatigue. Across all patients at all doses, there was a low incidence of skin rash of any form, eye disorders, neuropathy of any form and no cases of pneumonitis in any patient at any dose. The most common Grade 3 or higher treatment-related adverse event was neutropenia: seven cases or 14%; four of these were at doses above the RP2Ds. There were three subjects with serious adverse events (SAEs) at or above Grade 3 that were drug related (6%). Of these, none was in the 5 mg/m2 cohort. Median percentage relative dose intensity was 99%, reflecting a low level of dose modifications especially for a Phase I dose escalation trial in a heavily pre-treated population.
BT8009 well tolerated at or below the two RP2Ds. At or below the RP2Ds of 5 mg/m2 weekly and 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle), treatment-related dose modifications were rare. There were no treatment-related discontinuations. The incidence of Grade 3 or higher related adverse events at or below the two RP2Ds was low. At the 5 mg/m2 weekly dose, there were no cases of Grade 3 or higher skin rash, eye disorders, neuropathy or pneumonitis.
Bicycle advancing BT8009 in ongoing expansion cohorts. In November 2022, Bicycle announced the dosing of the first patient in the part B dose expansion portion of the Phase I/II trial. Up to 66 patients will be enrolled in the initial monotherapy expansion cohorts, with the ability to further expand enrollment based on results from these cohorts. These monotherapy cohorts include urothelial cancer patients who are enfortumab vedotin (EV) naïve and those who are EV exposed, as well as cohorts in ovarian, triple negative breast and non-small cell lung cancers. A Phase II trial of BT8009 in combination with pembrolizumab remains on track to commence this year.

Poster Presentation Details

Title: BT8009-100: A Phase I/II Study of a Novel Bicyclic Peptide and MMAE Conjugate BT8009 in Patients with Advanced Malignancies Associated with Nectin-4 Expression, Including Urothelial Cancer
Abstract #: 498
Presenter: Capucine Baldini, M.D., on behalf of the BT8009-100 investigators
Session Title: Poster Session B: Prostate Cancer and Urothelial Carcinoma
Date/Time: Friday, February 17, 3:30 p.m. to 5:00 p.m.; 8:15 p.m. to 9:15 p.m. ET

Conference Call Details

Bicycle Therapeutics will host a conference call and webcast today, February 14, 2023 at 8:00 a.m. ET to review the data being presented. To access the call, please dial (866) 652-5200 (domestic) or (412) 317-6060 (international) and provide the Conference ID 10174689. A live webcast of the presentation will be available on the Investors & Media section of the Bicycle website, bicycletherapeutics.com.

On February 14, 2023 Theratechnologies Inc. (TSX: TH) (NASDAQ: THTX) ("Theratechnologies"), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported that it will report financial results for its fourth quarter and full year fiscal 2022 ended November 30, on Tuesday, February 28, 2023 (Press release, Theratechnologies, FEB 14, 2023, View Source [SID1234627181]).

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The conference call will be held at 8:30 a.m. (ET) on February 28, 2023, to discuss the results and recent business updates. The call will be hosted by Paul Lévesque, President and Chief Executive Officer. Joining Mr. Lévesque on the call will be other members of the management team, including Chief Financial Officer Philippe Dubuc, Chief Medical Officer Christian Marsolais, and Chief Commercial Officer John Leasure, who will be available to answer questions from participants following prepared remarks.

Participants are encouraged to join the call at least ten minutes in advance to secure access.

Conference call dial-in and replay information is below:

CONFERENCE CALL INFORMATION
Conference Call Date: February 28, 2023
Conference Call Time: 8:30 AM ET
North America Dial-in: 1- 877-513-4119
International Dial-in: 1- 412-902-6615
Access Code: 2102918
CONFERENCE CALL REPLAY
North America Dial-in: 1- 877-344-7529
International Dial-in: 1- 412-317-0088
Replay Access Code: 3648244
Replay End Date March 07, 2023

The live conference call will be accessible via webcast at:
View Source

On February 14, 2023 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, reported that, on February 9, 2023, the Compensation Committee of Precision’s Board of Directors approved the grant of inducement awards to new employees under the Precision BioSciences, Inc. 2021 Employment Inducement Incentive Award Plan ("Inducement Award Plan") (Press release, Precision Biosciences, FEB 14, 2023, View Source [SID1234627179]). The inducement awards consist of options to purchase ("stock options") an aggregate of 159,097 shares of Precision’s common stock, par value $0.000005 (the "Common Stock"), which stock options were granted among eight employees who commenced employment between October 31, 2022 and January 23, 2023. Each of the stock options were granted under Nasdaq Listing Rule 5635(c)(4) as an inducement for the employees to commence service with Precision.

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The stock options have a per share exercise price equal to the fair market value of Precision’s Common Stock on the grant date, which was equal to $1.13. Each of the stock options has a 10-year term and vests (subject to continued service to Precision through the applicable vesting dates) as to 25% of the award on the first anniversary of the date of the commencement of their employment and, as to the remaining 75%, in substantially equal quarterly installments over the three years thereafter.

On February 14, 2023 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to develop and launch the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, reported recent corporate highlights and financial results for its fiscal first quarter ended December 31, 2022 (Press release, Outlook Therapeutics, FEB 14, 2023, View Source [SID1234627178]).

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Recent Corporate Highlights

Strengthened Medical Affairs and Commercial Expertise with Appointments of Surendra Sharma, MD, Senior Vice President of Medical Affairs, and Glen Olsheim, Executive Director of Commercial Excellence.
Closed on approximately $54 million in net proceeds from two financings to support pre-launch commercial activities through anticipated FDA approval of ONS-5010 in third calendar quarter of 2023 and into the fourth calendar quarter of 2023.
Approximately $24 million registered direct equity offering priced at-the-market under Nasdaq rules.
Approximately $30 million net proceeds from issuance of an unsecured convertible promissory note with an initial conversion price of $2.00 per share.
Received validation of Marketing Authorization Application (MAA) by the European Medicines Agency (EMA) for ONS-5010/ LYTENAVA (bevacizumab-vikg).
Announced that the FDA accepted its Biologics License Application (BLA) for ONS-5010 / LYTENAVA (bevacizumab-vikg) for the treatment of wet AMD and set a PDUFA goal date of August 29, 2023.
"Our first fiscal quarter of 2023 continued to demonstrate solid execution toward the potential commercialization of ONS-5010. With the accepted FDA filing of our BLA for ONS-5010 and PDUFA date set for August 29, 2023, and review of our MAA in the EU underway with a decision date expected in early 2024, we are well on our way toward our goal of becoming a commercial-stage company," commented Russell Trenary, President and Chief Executive Officer of Outlook Therapeutics. "Looking ahead, we remain focused on execution and positioning ourselves for a commercial launch of ONS-5010 to enhance the standard of care in the retinal anti-VEGF space."

ONS-5010 / LYTENAVA (bevacizumab-vikg) Pre-Launch Commercial Planning Underway

According to GlobalData, the use of unapproved repackaged IV bevacizumab from compounding pharmacies is estimated to account for approximately 50% of all wet AMD injections in the United States each year. Globally, the nine major markets account for an estimated $13.1 billion market for anti-VEGF drugs to treat retina diseases.

In anticipation of potential FDA marketing approval in 2023, Outlook Therapeutics has begun commercial launch planning, including best-in-class partnerships with FUJIFILM Diosynth Biotechnologies for drug substance, and with drug product manufacturer Aji Bio-pharma Services for the finished drug product.

Outlook Therapeutics is actively building out its sales and commercial team, and in September 2022, Outlook Therapeutics entered into a strategic partnership with AmerisourceBergen in preparation for the anticipated commercial launch in the United States of ONS-5010. As Outlook Therapeutics moves toward a potential launch in the United States, AmerisourceBergen’s commercialization support will expand to include additional services. Through the agreement with AmerisourceBergen, Outlook Therapeutics expects to significantly increase market access and efficient distribution of ONS-5010, if approved by the FDA. Moreover, working with AmerisourceBergen will help to provide Outlook Therapeutics with an accelerated pathway to deliver a high-quality customer experience to retina specialists. To bring ONS-5010 to market in a way that benefits all stakeholders – patients, clinicians, and payors – Outlook Therapeutics has also been in collaborative discussions with payors and the retina community.

Outlook Therapeutics is also developing registration documents on a parallel path for approvals in Europe and submitted them in December 2022. The formal review process of the MAA by the EMA’s Committee for Medicinal Products for Human Use (CHMP) is underway with an estimated decision date expected in early 2024. In addition to pursuing potential strategic partnering opportunities in the EU and other regions, such as the current partnership with Syntone Biopharma JV in China, Outlook Therapeutics is also exploring an expanded relationship with AmerisourceBergen to support the launch of ONS-5010 in international markets. AmerisourceBergen increased its global distribution capabilities in 2021 with the acquisition of Alliance Healthcare, a leading wholesaler of healthcare products in Europe.

In addition to the clinical development program evaluating ONS-5010 for wet AMD, Outlook Therapeutics has received agreements from the FDA on three Special Protocol Assessments (SPAs) for three additional registration clinical trials. These SPAs cover the protocols for a planned registration clinical trial evaluating ONS-5010 to treat branch retinal vein occlusion (BRVO), NORSE FOUR, and two planned registration clinical trials evaluating the drug candidate for the treatment of diabetic macular edema (DME), NORSE FIVE and NORSE SIX.

Upcoming Anticipated Milestones

Continued progress with ongoing pre-launch commercial preparations in anticipation of potential approval for ONS-5010 in 2023;
PDUFA goal date of August 29, 2023;
Completion of enrollment in the NORSE SEVEN clinical trial assessing the safety of ONS-5010 in a pre-filled syringe; and
Estimated decision date from the EMA’s CHMP on the Company’s submitted MAA in EU for ONS-5010 expected in early 2024.
Financial Highlights for the Fiscal First Quarter Ended December 31, 2022

For the fiscal first quarter ended December 31, 2022, Outlook Therapeutics reported a net loss attributable to common stockholders of $18.7 million, or $0.08 per basic and diluted share, compared to a net loss attributable to common stockholders of $14.5 million, or $0.08 per basic and diluted share, for the same period last year.

In December 2022, the Company closed a registered direct equity offering priced at-the-market under Nasdaq rules, resulting in net proceeds of approximately $24.0 million. Additionally, the Company closed on an unsecured convertible promissory note (the "Note") with a face amount of $31.8 million and net proceeds of approximately $30.0 million after original issue discount and after deducting the lender’s transaction costs. The net proceeds from these transactions are expected to provide sufficient capital to support operations past the anticipated FDA approval of ONS-5010 in the third calendar quarter of 2023 and into the fourth calendar quarter of 2023.

At December 31, 2022, Outlook Therapeutics had cash and cash equivalents of $52.3 million.

About ONS-5010 / LYTENAVA (bevacizumab-vikg)

ONS-5010 is an investigational ophthalmic formulation of bevacizumab under development as an intravitreal injection for the treatment of wet AMD and other retinal diseases. Because no currently approved ophthalmic formulations of bevacizumab are available, clinicians wishing to treat retinal patients with bevacizumab have had to use unapproved repackaged IV bevacizumab provided by compounding pharmacies, products that have known risks of contamination and inconsistent potency and availability. If approved, ONS-5010 can replace the need to use unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.

Bevacizumab-vikg is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab-vikg to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.