On August 3, 2023 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported financial results for the second quarter ended June 30, 2023, and provided a corporate update (Press release, Prelude Therapeutics, AUG 3, 2023, View Source [SID1234633766]).

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Kris Vaddi, Ph.D., Chief Executive Officer of Prelude stated, "With the recent financing that extended our cash runway into 2026, we are in a strong position to advance our diverse pipeline of potentially best and/or first-in-class compounds to address the needs of patients with certain underserved cancers. Our focus remains on generating critical data for each of our molecules to make key strategic decisions. As disclosed recently, and based on additional data generated in this quarter, PRT2527 (CDK9 inhibitor) and PRT1419 (MCL1 inhibitor) demonstrated differentiated clinical safety profiles and strong target inhibition and are continuing to enroll patients with hematological malignancies, which is where we see the best opportunities for these molecules."

"Our first-in-class selective SMARCA2 degrader, PRT3789, and next generation CDK4/6 inhibitor, PRT3645, are progressing well in Phase 1 and are on track to reach confirmation doses in the first half of 2024 and by year end 2023, respectively," added Dr. Vaddi. "Based on meaningful progress made in the first half of the year, we look forward to sharing updates and clarity around strategic prioritization of our pipeline in the coming months."

Pipeline Updates

PRT2527- CDK9 Inhibitor Program

The Company believes its highly selective CDK9 inhibitor, PRT2527, has the potential to avoid off-target toxicities, achieve substantial clinical activity and become the best-in-class CDK9 inhibitor, making it amenable for combination with other therapies.

PRT2527 has completed a Phase 1 multi-dose escalation study (NCT05159518) in patients with solid tumors. In this trial, PRT2527 was shown to achieve high levels of target inhibition and the potential to be better tolerated than existing CDK9 inhibitors, specifically, manageable neutropenia and an absence of meaningful gastrointestinal events or hepatotoxicity. *

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AACR2023 Poster Presentation

A Phase 1 multi-dose escalation study (NCT05665530) is currently ongoing in hematologic malignancies. Patient recruitment for hematological clinical trials in the US is highly competitive and this trial has recently been expanded to include global sites to support patient recruitment.

The Company’s objective is to establish a biologically active confirmation dose by Q1 2024. As part of this Phase 1 multi-dose escalation trial, the Company intends to expand the Phase 1 clinical trial and evaluate PRT2527 in combination with zanubrutinib.

Potential indications for PRT2527 include aggressive B-cell lymphoma subtypes, mantle cell lymphoma (MCL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) including Richter syndrome, and T-cell lymphoma subtypes.

The Company intends to provide a program update by year end on the CDK9 inhibitor program and present initial results at a future scientific meeting.

PRT1419- MCL1 Inhibitor Program

PRT1419 is a potent and selective MCL1 inhibitor. With its optimized PK/PD profile, the Company believes PRT1419 has the potential to achieve greater target engagement and provide patients with better clinical outcomes as well as improved safety and tolerability, as compared to other MCL1 inhibitors in development.

PRT1419 has completed a Phase 1 multi-dose escalation study (NCT04837677) in patients with solid tumors. In this study, PRT1419 demonstrated an acceptable safety and tolerability profile in patients with advanced and metastatic solid tumors. No cardiac toxicity was observed. Pharmacokinetics/pharmacodynamics and safety data in the 80 mg/m2 QW dose cohort support further evaluation of this dose in future studies.

A Phase 1 multi-dose escalation clinical trial of PRT1419 in patients with hematologic malignancies is ongoing (NCT05107856). In this trial, PRT1419 is being evaluated as monotherapy for myeloid malignancies and in combination with azacitidine or venetoclax for patients with relapsed/refractory myeloid or B-cell malignancies.

The Company will provide a clinical update on PRT1419 by year end.

PRT3645- Next Generation CDK4/6 Inhibitor Program

PRT3645 is a highly potent and selective next generation CDK4/6 inhibitor with the potential to provide improved safety and tolerability outcomes and higher, more effective brain and tissue penetration than current CDK4/6 inhibitors.

In preclinical models in vivo, PRT3645 has been shown to be efficacious in multiple cancers as monotherapy as well as when combined with KRAS inhibitors, MEK inhibitors and with a brain penetrant HER2 receptor kinase inhibitor. Additionally, oral administration of PRT3645 has been shown to induce tumor regressions in preclinical models that are resistant to currently approved CDK4/6 inhibitors. Together, these data suggest that PRT3645 may extend the benefit of CDK4/6 inhibition beyond HR+ breast cancer.

A Phase 1 multi-dose escalation clinical trial of PRT3645 (NCT05538572) is underway and the Company expects to reach a biologically active dose confirmation in Q4 2023.

Potential indications for PRT3645 in combination with other therapies, in addition to breast cancer with or without brain metastases, include endometrial, sarcomas, glioblastomas, non-small cell lung cancer, head and neck cancers.

The Company intends to provide a program update by year end and present initial results at a future scientific meeting.

PRT3789- SMARCA2 Targeted Protein Degrader Program

PRT3789 is a first-in-class highly selective degrader of SMARCA2 protein, which along with SMARCA4 controls gene regulation through chromatin remodeling. Cancer cells with SMARCA4 mutations are dependent on SMARCA2 for their growth and survival and selectively degrading SMARCA2 induces cell death in cancer cells while sparing normal cells. PRT3789 is efficacious and well tolerated in preclinical models of SMARCA4 deleted/mutated cancers as monotherapy and in combination with standards of care. The Company believes a selective SMARCA2 degrader has the potential to be of benefit in up to 70,000 US/EU cancer patients with the SMARCA4 mutation.

Patients with SMARCA4 mutations or deletions may have poor clinical outcomes and limited treatment options. Therefore, mutated, or deleted SMARCA4 cancers provides a potential biomarker to select those patients most likely to respond to treatment with a highly selective SMARCA2 degrader.

A Phase 1 multi-dose escalation clinical trial of PRT3789 is ongoing (NCT05639751) in biomarker selected SMARCA4 mutated cancers. The Company intends to evaluate PRT3789 as monotherapy as well as in combination.

The Company intends to provide a program update by year end and expects to reach confirmation dose in the first half of 2024.

SMARCA2- Oral Program

The Company has also recently nominated a new chemical entity as a potent, orally bioavailable and highly selective SMARCA2 degrader candidate (>1000x over SMARCA4) and intends to file an IND early in 2024.

Second Quarter 2023 Financial Results

Cash, Cash Equivalents and Marketable Securities: In May 2023, the Company completed a public offering of common stock, raising gross proceeds of $113.0 million before deducting underwriting discounts, commissions and offering expenses. Net proceeds received, $110.4 million, will be focused on the continued development and expansion of the Company’s product pipeline.

Cash, cash equivalents, and marketable securities as of June 30, 2023, were $255.0 million. Prelude anticipates that its existing cash, cash equivalents and marketable securities will fund the Company’s operations into 2026.

Research and Development (R&D) Expenses: For the second quarter of 2023, R&D expense increased to $25.0 million from $21.3 million for the prior year period. Research and development expenses increased primarily due to the timing of our clinical research programs. We expect our R&D expenses to vary from quarter to quarter, primarily due to the timing of our clinical development activities.

General and Administrative (G&A) Expenses: For the second quarter of 2023, G&A expenses decreased to $7.4 million from $8.2 million for the prior year period. General and administrative expenses decreased reflecting the Company’s careful management of its G&A expenses.

Net Loss: For the three months ended June 30, 2023, net loss was $30.4 million, or $0.54 per share compared to $27.4 million, or $0.58 per share, for the prior year period. Included in the net loss for the quarter ended June 30, 2023, was $6.7 million of non-cash expense related to the impact of expensing share-based payments, including employee stock options, as compared to $6.0 million for the same period in 2022.

On August 3, 2023 OPKO Health, Inc. (NASDAQ: OPK) reported business highlights and financial results for the three and six months ended June 30, 2023 (Press release, Opko Health, AUG 3, 2023, View Source [SID1234633765]).

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Second quarter business highlights included the following:

U.S. FDA approved NGENLA for pediatric growth hormone deficiency; OPKO earned a $90 million milestone payment from its commercial partner, Pfizer. In June 2023, the U.S. Food and Drug Administration (FDA) approved NGENLA (somatrogon), a once-weekly, human growth hormone analog indicated for the treatment of pediatric patients aged three years and older with impaired growth due to insufficient growth hormone. Pfizer, OPKO’s commercial partner, expects NGENLA to become available for U.S. prescribing this month. In addition to the $90 million milestone payment earned upon receipt of FDA approval, OPKO is entitled to profit sharing based on regional, tiered gross profit for both NGENLA and Genotropin, Pfizer’s daily human growth hormone.
NGENLA has now been approved in 44 markets including the U.S., Japan, EU Member States, Canada and Australia; sales are underway by Pfizer in over 18 countries with expectations to launch in all priority international markets by year-end. NGENLA is the first once-weekly product approved for the treatment of pediatric growth hormone deficiency in Japan, Canada, Australia, the United Kingdom, Taiwan, United Arab Emirates and Brazil. OPKO is entitled to gross profit sharing in all global markets based on regional, tiered gross profit for both NGENLA and Genotropin, with the U.S. region commencing gross profit sharing in August 2023.
OPKO Health’s ModeX Therapeutics, Inc. (ModeX) advanced its antiviral and immune-oncology product pipeline. ModeX continued to advance its pipeline of antiviral and immune-oncology programs utilizing its next-generation multispecific antibodies, and anticipates initiating a Phase 1 clinical trial for certain cancers next year. In addition, ModeX’s collaboration with Merck to develop MDX-2201, its vaccine for Epstein-Barr virus, is progressing. As part of its ongoing business strategy, ModeX is pursuing additional licensing and collaboration opportunities with strategic partners for certain other pipeline candidates.

BioReference Health continued on its path to profitability with cost reductions, improved operational efficiencies and enhanced productivity. BioReference continued to implement initiatives to reduce costs and rationalize its business in line with current testing volumes. Additionally, BioReference is focused on improving productivity and enhancing innovation of its higher value specialty testing segments. Other efforts to return this business to profitability include expanding into new market segments, such as providing information for the pharmaceutical market.
Second Quarter Financial Results

Pharmaceuticals: Revenue from products in the second quarter of 2023 increased to $43.5 million from $35.9 million in the second quarter of 2022, driven by sales in OPKO’s international operating companies and an increase in sales of Rayaldee to $7.7 million from $6.2 million in the prior-year period. Revenue from the transfer of intellectual property was $94.9 million in the second quarter of 2023, reflecting revenue of $90.0 million triggered by the FDA approval of NGENLA, compared with $87.2 million in the 2022 period, which included an $85.0 million milestone payment related to the commencement of NGENLA sales in Europe and Japan. Total costs and expenses were $74.7 million in the second quarter of 2023, up from $67.7 million in the prior-year period. The increase was mainly due to an increase in cost of revenue and a full quarter of research expenses at ModeX, which was acquired in May 2022. Operating income was $63.6 million in the second quarter of 2023, compared with $55.4 million in the second quarter of 2022.

Diagnostics: Revenue from services in the second quarter of 2023 was $127.0 million compared with $186.8 million in the prior-year period. Revenue decreased due to lower COVID-19 testing volume and reimbursement. BioReference processed approximately 33,000 COVID-19 PCR tests in the second quarter of 2023, representing 1.5% of total testing volume, versus 874,000 tests in the second quarter of 2022, representing 31% of total testing volume. Furthermore, revenue during the 2022 period included $12.1 million from GeneDx, which was sold in April 2022. Total costs and expenses were $171.3 million in the second quarter of 2023 compared with $244.3 million in the second quarter of 2022, resulting in an operating loss of $44.3 million compared with an operating loss of $57.5 million in the 2022 period. The 2022 period included a $15.4 million gain on the sale of GeneDx offset by $5.8 million of operating losses prior to closing in April 2022. BioReference continues to implement cost-reduction initiatives as it works toward profitability.

Consolidated: Consolidated total revenues for the second quarter of 2023 were $265.4 million compared with $309.9 million for the comparable period of 2022. Operating income for the second quarter of 2023 was $7.0 million compared with an operating loss of $10.7 million for the 2022 quarter. Net loss for the second quarter of 2023 included a mark-to-market adjustment of $19.9 million compared to $71.2 million in the 2022 period related to the decrease in share price of GeneDx, resulting in a net loss of $19.6 million, or $0.03 per share, compared with a net loss of $101.7 million, or $0.14 per share, for the 2022 quarter.

Cash and cash equivalents: Cash and cash equivalents were $108.1 million as of June 30, 2023, which does not include the $90.0 million milestone payment from Pfizer that is expected to be received in August 2023.
Conference Call and Webcast Information

OPKO’s senior management will provide a business update, discuss second quarter financial results, provide financial guidance and answer questions during a conference call and audio webcast today beginning at 4:30 p.m. Eastern time. Participants are encouraged to pre-register for the conference call here. Callers who pre-register will receive a unique PIN to gain immediate access to the call and bypass the live operator. Participants may register at any time, including up to and after the call start time. Those unable to pre-register may participate by dialing 833-630-0584 (U.S.) or 412-317-1815 (International). A webcast of the call can also be accessed at OPKO’s Investor Relations page and here.

A telephone replay will be available until August 10, 2023 by dialing 877-344-7529 (U.S.) or 412-317-0088 (International) and providing the passcode 7009686. A webcast replay will be available beginning approximately one hour after the completion of the live conference call here.

On August 3, 2023 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the receipt of a Study May Proceed letter from the U.S. Food and Drug Administration (FDA), for a Phase 1/2 dose escalation study of ONCT-534, a novel dual-action androgen receptor inhibitor (DAARI), in patients with metastatic castration-resistant prostate cancer (mCRPC) who have relapsed or are refractory to approved androgen receptor signaling inhibitors (ARSIs) (Press release, Oncternal Therapeutics, AUG 3, 2023, View Source [SID1234633764]). The letter was received prior to the 30-day review date.

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"We are very pleased with the FDA’s authorization to proceed with our Phase 1/2 clinical trial of ONCT-534," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "Many men suffering from prostate cancer that has relapsed or is refractory after treatment with standard of care ARSI therapy, such as enzalutamide or abiraterone, need additional treatment alternatives. We believe that ONCT-534’s novel mechanism of action may help address key tumor escape mechanisms that cause such resistance. Preclinical studies suggest that ONCT-534 binds to both the ligand-binding domain (LBD) and N-terminal domain of the androgen receptor (AR), inhibiting AR function and triggering AR protein degradation, even in the presence of ligand-binding domain alterations including mutations and splice variants such as AR-V7. Clinical sites that will conduct the initial dose finding study for ONCT-534 have been selected and we expect to report preliminary data in the first half of 2024".

On August 3, 2023 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported its participation at an upcoming investor conference (Press release, Nkarta, AUG 3, 2023, View Source [SID1234633762]):

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Canaccord Genuity 43RD Annual Growth Conference
August 10, 2023
12:00 p.m. ET – fireside chat

A simultaneous webcast of each event will be available on the Investors section of Nkarta’s website, www.nkartatx.com, and a replay will be archived on the website for approximately 90 days.

On August 3, 2023 NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class immunomedicines to treat cancer and other immune-related diseases reported a business update and provided second quarter 2023 financial results (Press release, NextCure, AUG 3, 2023, View Source [SID1234633761]).

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"As we enter the remainder of 2023, we continue generating important data and are nearing updates on our clinical programs expected in the fourth quarter of this year," said Michael Richman, NextCure’s president and chief executive officer. "We expect to continue to advance our programs while prudently managing our resources to support our financial runway into mid-2025."

Q2 2023 Business Highlights and Near-Term Milestones

NC410 (LAIR-2 fusion)

● Continued enrollment in the Phase 1b/2 clinical trial evaluating NC410 in combination with pembrolizumab in patients with immune checkpoint naive or checkpoint refractory solid tumors.
● Phase 1b data are expected in the fourth quarter of 2023.

NC762 (B7-H4 mAb)

● Continued enrollment in the Phase 1b dose expansion study in patients with solid tumors and high expression of B7-H4.
● Phase 1b update is expected in the fourth quarter of 2023.

NC525 (LAIR-1 mAb)

● Continued enrollment in the Phase 1 monotherapy dose escalation and safety study evaluating NC525 in AML patients.
● Phase 1a update is expected in the fourth quarter of 2023.

NC318 (Siglec-15)

● Yale Cancer Center to present in September, "NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC", at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer in Singapore.

Financial Guidance

● NextCure expects its existing cash, cash equivalents and marketable securities will enable it to fund operating expenses and capital expenditures into mid-2025.

Financial Results for Quarter Ended June 30, 2023

● Cash, cash equivalents, and marketable securities as of June 30, 2023, were $130.6 million as compared to $159.9 million as of December 31, 2022. The decrease of $29.3 million was primarily related to cash used to fund operations, and cash used to purchase fixed assets.
● Research and development expenses were $13.4 million for the quarter ended June 30, 2023, as compared to $12.8 million for the quarter ended June 30, 2022. The increase of $0.6 million was primarily related to higher clinical costs.
● General and administrative expenses were $5.7 million for the quarter ended June 30, 2023, as compared to $5.3 million for the quarter ended June 30, 2022. The increase of $0.4 million was primarily related to higher payroll and legal costs partially offset by lower stock compensation costs and lower insurance costs.
● Net loss was $17.9 million for the quarter ended June 30, 2023, as compared with a net loss of $17.9 million for the quarter ended June 30, 2022. Higher research and development expenses and higher general and administrative expenses were offset by higher other income, primarily interest income.