Morphic Announces Corporate Highlights and Financial Results for the Second Quarter 2022

On August 3, 2022 Morphic Therapeutic (Nasdaq: MORF), a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, reported corporate highlights and financial results for the second quarter of 2022 (Press release, Morphic Therapeutic, AUG 3, 2022, View Source [SID1234617384]).

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Second Quarter 2022 and Recent Corporate Highlights

Continued enrollment of EMERALD-1 (MORF-057-201) phase 2a study
EMERALD-1, an open-label multi-center study of MORF-057 enrolling up to 35 patients with moderate to severe ulcerative colitis (UC), who will receive 100 mg BID (twice daily), continues to progress as planned
EMERALD-2 (MORF-057-202), a global phase 2b double-blind randomized placebo-controlled trial of MORF-057, is now expected to begin in the fourth quarter of 2022 and top line results are expected in the first half of 2025
Announced several key leadership appointments and promotions
Appointed Joanne Gibbons as Senior Vice President of Regulatory Affairs
Ms. Gibbons has nearly 25 years of experience in Regulatory Affairs and Clinical Development, both in the development of novel drugs and the expansion of marketed products
Named Dr. Bruce Rogers as President of Morphic Therapeutic
Dr. Rogers previously served as Morphic’s Chief Scientific Officer from 2016
Dr. Rogers has over 25 years of biopharmaceutical experience, including 18 years of experience in roles of increasing responsibility at Pfizer
Named Dr. Blaise Lippa as Chief Scientific Officer of Morphic
Dr. Lippa previously served as Morphic’s Senior Vice President of Molecular Discovery and was part of the founding team at Morphic
Dr. Lippa has over 20 years of experience in the biopharmaceutical industry, including time at Pfizer and Cubist, prior to its acquisition by Merck
Advanced the Company’s research and development collaboration with Janssen, focused on an antibody activator of a high potential integrin target
Concluded the Company’s research and development collaboration efforts with AbbVie
Morphic successfully delivered on the terms of the AVB6 collaboration and Morphic and AbbVie are in the process of drafting a joint publication for the AVB6 program
"Morphic is confidently climbing through a vital period in our development as the EMERALD clinical trials of MORF-057 in UC move forward flat out," commented Praveen Tipirneni, MD, Chief Executive Officer of Morphic Therapeutic. "The EMERALD-1 phase 2a study is progressing according to plan and our esprit de corps continues to strengthen through several senior appointments. Most notably, we announced the promotion of two key longstanding and high performing executives, Bruce Rogers and Blaise Lippa, and the addition of our new SVP of Regulatory Affairs, Joanne Gibbons. With the additional capital raised in the second quarter and refined operating plans, we have bolstered our financial position and extended our cash-runway into 2025, well after the primary endpoint readout of the EMERALD-2 phase 2b study."

Financial Results for the Second Quarter 2022

Net income for the quarter ended June 30, 2022 was $26.8 million or $0.68 per share compared to a net loss of $27.8 million or $0.77 per share for the same quarter last year
Revenue was $60.2 million for the quarter ended June 30, 2022, compared to $3.8 million for the same quarter last year. The increase was primarily due to the forthcoming conclusion of the collaboration with AbbVie which resulted in $57.7 million recognition of collaboration revenue in the quarter ended June 30, 2022
Research and development expenses were $25.7 million for the quarter ended June 30, 2022, as compared to $24.6 million for the same quarter last year. The increase was primarily attributable to higher clinical and development costs along with higher pre-clinical and phase 2 clinical trial costs to support our lead product candidate MORF-057
General and administrative expenses were $8.2 million for the quarter ended June 30, 2022, compared to $7.1 million for the same quarter last year. The increase was due to increased non-cash stock-based compensation expense and higher payroll costs
As of June 30, 2022, Morphic had cash, cash equivalents and marketable securities of $397.6 million, compared to $380.7 million as of March 31, 2022. We have updated our current operating plan with the receipt of $39.2 million in net proceeds raised under our ATM; the focusing and reduction in the scope of our partnered programs; a proactive pipeline prioritization and the implementation of increased operational efficiencies. Morphic believes its cash, cash equivalents and marketable securities as of June 30, 2022, will be sufficient to fund operating expenses and capital expenditure requirements into the second half of 2025.

MorphoSys AG Reports Second Quarter and First Half 2022 Financial Results

On August 3, 2022 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported that results for the second quarter and first half year of 2022 (Press release, MorphoSys, AUG 3, 2022, View Source [SID1234617421]).

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"In the second quarter of 2022 we made important progress in advancing patient enrollment across our pivotal phase 3 studies and commercializing Monjuvi, where we observed a bounce back in sales following a challenging first quarter", said Jean-Paul Kress, M.D., Chief Executive Officer of MorphoSys. "Despite the reduced guidance update, we anticipate Monjuvi growth to continue into the second half of the year and beyond. We remain well capitalized to get through important clinical milestones, potentially bringing new effective blood cancer medicines to patients and generating significant value for our shareholders."

Tafasitamab Highlights:

Monjuvi (tafasitamab-cxix) U.S. net product sales of US$ 23.3 million (€ 21.7 million) for the second quarter 2022 (Q2 2021: US$ 18.0 million (€ 14.9 million)) and US$ 41.9 million (€ 38.3 million) for the first half of 2022.

Minjuvi royalty revenue of € 0.7 million for sales outside of the U.S. in the second quarter 2022 and € 1.4 million for the first half of 2022.

Pfizer, Incyte and MorphoSys signed a clinical trial collaboration and supply agreement on June 13, 2022, to investigate the immunotherapeutic combination of Pfizer’s TTI-622, a novel SIRPα-Fc fusion protein, and Monjuvi plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT).

Other highlights:

Pelabresib data presented at EHA (Free EHA Whitepaper) Congress 2022: Efficacy and safety data from the ongoing phase 2 MANIFEST trial of pelabresib in myelofibrosis and translational research findings suggesting the potential disease-modifying effect of pelabresib in patients with myelofibrosis were presented in oral presentations at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 (EHA 2022) Hybrid Congress.

Agreement with HIBio on felzartamab and MOR210: Human Immunology Biosciences, Inc. (HIBio) signed an equity participation agreement and license agreements with MorphoSys to allow HIBio to develop and commercialize MorphoSys’ felzartamab, an anti-CD38 antibody, and MOR210, an anti-C5aR1 antibody across all indications worldwide, with the exception of Greater China for felzartamab and Greater China and South Korea for MOR210. As part of the agreements, MorphoSys will receive a 15% equity stake in HIBio, along with certain equity earn-in provisions and standard investment rights. On achievement of development, regulatory and commercial milestones, MorphoSys will be eligible to receive payments from HIBio of up to US$ 1 billion across both programs, in addition to tiered, single- to low double-digit royalties on net sales of felzartamab and MOR210. Upon signing, MorphoSys also received an upfront payment of US$ 15 million for MOR210. HIBio has full responsibility for future development and commercialization of felzartamab and MorphoSys will transfer the development candidate and the clinical studies over to HIBio in the next months. MorphoSys will be compensated for ongoing program expenses for felzartamab during this program transition period by HIBio.

Significant Events After the End of the Second Quarter of 2022:

On July 26, 2022, MorphoSys notified Royalty Pharma that it intends to draw US$ 300.0 million (€ 296.3 million) of the development funding bond. The proceeds are anticipated to be delivered to MorphoSys in September 2022 and will be used primarily to fund development activities.

Financial Results for the Second Quarter of 2022 (IFRS):

Revenues for the second quarter 2022 were € 59.4 million compared to € 38.2 million for the same period in 2021. The year-over-year growth in Monjuvi product sales was driven by higher demand.

Cost of Sales: In the second quarter 2022, cost of sales were € 17.2 million compared to € 10.1 million for the comparable period in 2021.

Research and Development (R&D) Expenses: In the second quarter 2022, R&D expenses were € 60.9 million compared to € 40.5 million in the second quarter 2021. The increase in R&D expenses is primarily due to the first-time inclusion of Research and Development expenses from Constellation from July 2021 on and higher investment to support the advancement of clinical programs.

Selling, General and Administrative (SG&A) Expenses: Selling expenses in the second quarter 2022 were € 24.0 million compared to € 28.5 million in the second quarter 2021. The decrease was driven by higher investments in 2021 made into the commercial organization, the first full year after the Monjuvi launch. General and administrative (G&A) expenses in the second quarter 2022 amounted to € 12.4 million compared to € 30.5 million in the second quarter 2021. The decrease was driven by the transaction costs for the Constellation acquisition and Royalty Pharma agreements executed in the second quarter 2021.

Operating Loss: Operating loss amounted to € 55.1 million in the second quarter 2022 (Q2 2021: operating loss of € 71.4 million).

Consolidated Net Loss: For the second quarter 2022, consolidated net loss was € 235.0 million (Q2 2021: consolidated net profit of € 20.9 million).

Financial Results for the first six months 2022 (IFRS):

Revenues for the first six months of 2022 were € 100.9 million (H1 2021: € 85.4 million). Revenues include € 38.3 million from the recognition of Monjuvi product sales in the U.S. Royalties in H1 2022 included € 1.4 million from the sale of Minjuvi outside of the U.S. by our partner Incyte and € 39.7 million from Tremfya sales which is fully passed onto Royalty Pharma.

Cost of Sales: For the first six months of 2022, cost of sales were € 25.1 million (H1 2021: € 15.2 million). The year-over-year increase was primarily driven by higher sales of Monjuvi in the U.S. and Minjuvi outside of the U.S.

R&D Expenses: In the first six months of 2022, R&D expenses were € 126.0 million compared to € 73.8 million for the same period in 2021. The R&D expenses increased due to inclusion of expenses from Constellation and higher investments to support the advancement of clinical programs.

SG&A Expenses: Selling expenses decreased in the first six months of 2022 to € 45.9 million compared to € 56.6 million for the same period in 2021. The year-over-year decrease was primarily driven by higher investments made in the commercial organization in 2021, the first full year after the Monjuvi launch. G&A expenses amounted to € 27.0 million in the first six months of 2022 compared to € 40.8 million for the same period in 2021. The year-over-year decrease was driven primarily by the transaction costs for the Constellation acquisition and Royalty Pharma agreements executed in the second quarter of 2021.

Operating Loss: Operating loss amounted to € 123.1 million in the first six months of 2022 (H1 2021: operating loss of € 101.0 million).

Consolidated Net Profit / Loss: For the first six months of 2022, consolidated net loss was € 357.6 million (H1 2021: consolidated net loss of € 20.7 million).

Cash and Other Financial Assets: As of June 30, 2022, the Company had cash and other financial assets of € 754.3 million compared to € 976.9 million on December 31, 2021. The Company anticipates proceeds of US$ 300.0 million in September 2022 from the development funding bond provided by Royalty Pharma.

Number of shares: The number of shares issued totaled 34,231,943 on June 30, 2022, remained unchanged since December 31, 2021.

Updated Full Year 2022 Financial Guidance:

The updated financial guidance was issued on July 26, 2022.

Amounts in million

Updated 2022
Financial Guidance

Previous* 2022
Financial Guidance

2022 Guidance Insights

Monjuvi U.S. Net Product Sales

US$ 90m to 110m

US$ 110m to 135m

100% of Monjuvi U.S. product sales are recorded on MorphoSys’ income
statement and related profit/loss is split 50/50 between MorphoSys and Incyte.

Gross Margin for Monjuvi U.S. Net Product Sales

75% to 80%

75% to 80%

100% of Monjuvi U.S. product cost of sales are recorded on MorphoSys’ income
statement and related profit/loss is split 50/50 between MorphoSys and Incyte.

R&D expenses

€ 275m to 300m

€ 300m to 325m

Reduction in guidance range driven primarily by license agreement for
felzartamab to HIBio executed on June 14, 2022.

SG&A expenses

€ 150m to 165m

€ 155m to 170m

53% to 58% of mid-point of SG&A expenses represent Monjuvi U.S. selling
costs of which 100% are recorded in MorphoSys’ income statement. Incyte reimburses
MorphoSys for half of these selling expenses.

*The Previous 2022 Financial Guidance was initially provided on January 7 and reiterated on March 16 and on May 4, 2022.

Additional information related to 2022 Financial Guidance:

Tremfya royalties will continue to be recorded as revenue without any cost of sales in MorphoSys’ income statement. These royalties, however, will not contribute any cash to MorphoSys as 100% of the royalties will be passed on to Royalty Pharma.
MorphoSys anticipates receiving royalties for Minjuvi sales outside of the U.S. Guidance for these royalties is not being provided as MorphoSys does not receive any sales forecasts from its partner Incyte.
MorphoSys does not anticipate any significant cash-accretive revenues from the achievement of milestones in 2022. Milestones for otilimab are passed on to Royalty Pharma. Milestones from all other programs remain with MorphoSys at 100%.
MorphoSys anticipates sales of commercial and clinical supply of tafasitamab outside of the U.S. to its partner Incyte. Revenue from this supply is recorded in the "Licenses, milestones and other" category in MorphoSys’ income statement. These sales result in a zero gross profit/margin. As such, MorphoSys does not provide guidance for these sales.
While R&D expense is anticipated to grow year-over-year due to investments in three pivotal studies, the growth is partially being offset by the consolidation of research/discovery activities.
SG&A expense guidance range reflects savings from synergies following the acquisition of Constellation and streamlined commercialization efforts.
Operational Outlook for 2022:

MorphoSys anticipates the following key development milestones in 2022:

First proof-of-concept data from the ongoing clinical phase 2 study of CPI-0209 in solid tumors and blood cancer;
MorphoSys’ partner Roche expects a pivotal data readout of the GRADUATE 1 and GRADUATE 2 trials with gantenerumab in the second half of 2022. Roche initiated these phase 3 development programs for patients with Alzheimer’s disease in 2018;
MorphoSys’ partner GSK expects a pivotal data readout of the phase 3 ContRAst program investigating otilimab for rheumatoid arthritis by the end of 2022.

*Value as of December 31, 2021

MorphoSys will hold its conference call and webcast on August 4, 2022, to present the results of the second quarter and first half of 2022 and the outlook for 2022.

Please dial in 10 minutes before the beginning of the conference.

A live webcast and slides will be made available at the Investors section under "Upcoming Events & Conferences" on MorphoSys’ website, View Source and after the call, a slide-synchronized audio replay of the conference will be available at the same location.

The statement for the second quarter/first half year of 2022 (IFRS) are available for download at: View Source

McKesson Corporation Reports Fiscal 2023 First-Quarter Results

On August 3, 2022 McKesson Corporation (NYSE:MCK) reported results for the first-quarter ended June 30, 2022 (Press release, McKesson, AUG 3, 2022, View Source [SID1234617444]).

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"McKesson had a solid start to fiscal 2023. Our results this quarter demonstrate the strength of our streamlined portfolio and successful execution as a diversified healthcare services company," said Brian Tyler, chief executive officer. "Our talented associates continue to deliver exceptional performance, and we remain confident that our strategy positions McKesson for long-term growth and value creation. As a result of our first-quarter operating performance and the continuation of COVID-19 response efforts, we are raising our guidance for fiscal 2023 Adjusted Earnings per Diluted Share to $23.95 to $24.65."

First-quarter revenues were $67.2 billion, an increase of 7% from a year ago, driven by growth in the U.S. Pharmaceutical segment, resulting from increased specialty product volumes, including retail national account customers, and market growth, partially offset by lower revenues in the International segment as a result of the planned progress with McKesson’s divestiture of its European businesses.

First-quarter earnings per diluted share from continuing operations was $5.25 compared to $3.09 a year ago, an increase of $2.16.

First-quarter Adjusted Earnings per Diluted Share was $5.83 compared to $5.56 a year ago, an increase of 5%, driven by growth across the North American businesses and a lower share count, partially offset by a higher tax rate and lower contribution from COVID-19 vaccine distribution, kitting, and storage programs with the U.S. government. First-quarter Adjusted Earnings per Diluted Share also included pre-tax net losses of approximately $22 million associated with McKesson Ventures’ equity investments, compared to pre-tax net gains of approximately $7 million in the first-quarter of fiscal 2022.

For the first three months of the fiscal year, McKesson returned $1.1 billion of cash to shareholders, which included $1.0 billion of common stock repurchases and $71 million of dividend payments. During the first three months of the fiscal year, McKesson used cash from operations of $941 million, and invested $100 million in capital expenditures, resulting in negative Free Cash Flow of $1.0 billion.

Capital Deployment Updates

McKesson maintains a disciplined approach to capital allocation, centered on delivering sustainable growth and long-term shareholder value. McKesson’s capital allocation framework consists of three pillars:

Prioritizing growth by investing internally and making acquisitions that support our strategic priorities.
Returning capital to shareholders through share repurchases and McKesson’s commitment to a growing dividend. Share repurchases are principally used to return cash to shareholders in absence of growth investment opportunities.
Maintaining a strong balance sheet, including strong Free Cash Flow generation, which provides ample liquidity and financial flexibility.
On July 22, 2022, McKesson’s Board of Directors declared a 15% increase to its quarterly dividend from $0.47 per share to $0.54 per share.

On July 22, 2022, McKesson’s Board of Directors authorized the company to repurchase up to an additional $4.0 billion of its common shares in a manner deemed in the best interest of the company and its stockholders, considering other growth opportunities and prevailing business and market conditions. Fiscal 2023 Adjusted Earnings per Diluted Share guidance continues to assume approximately $3.5 billion of share repurchases.

Business Highlights

Oncology: On June 23, 2022, McKesson announced an agreement to form a joint venture combining McKesson’s U.S. Oncology Research and HCA Healthcare’s Sarah Cannon Research Institute. Together, the joint venture will create a fully integrated oncology research organization aimed at expanding clinical research, accelerating drug development, and increasing availability and access to clinical trials for community oncology providers and patients, including those in underserved communities. The transaction is anticipated to close in 2022.
Europe: McKesson progressed in its planned exit of business operations within the European region and has completed divestitures or entered into agreements to sell 11 of the 12 countries.
After entering into an agreement in June 2022 to sell its Denmark business to Erhvervsinvest, McKesson closed the transaction on July 29, 2022.
After entering into an agreement in November 2021 to sell its UK business to AURELIUS, McKesson closed the transaction on April 6, 2022.
In July 2021, McKesson announced an agreement to sell certain McKesson Europe businesses in France, Italy, Ireland, Portugal, Belgium, and Slovenia to the PHOENIX Group. The transaction is expected to close in the second half of fiscal 2023.
Norway remains the only country that McKesson has not entered into an agreement to sell.
COVID-19: McKesson continues to play a leading role in the fight against COVID-19. McKesson renewed its partnership with the U.S. government to support the COVID-19 response efforts. The vaccine distribution contract has been extended through July 2023; and the kitting, storage, and distribution of ancillary supplies contract has been extended through January 2023.
U.S. Pharmaceutical Segment

First-quarter revenues were $56.9 billion, an increase of 14%, resulting from increased specialty product volumes, including retail national account customers, and market growth, partially offset by branded to generic conversions.
First-quarter Segment Operating Profit was $696 million. Adjusted Segment Operating Profit was $711 million, an increase of 4%, driven by growth in distribution of specialty products to providers and health systems, partially offset by lower demand of COVID-19 vaccine distribution. Excluding the impact of COVID-19 vaccine distribution, the U.S. Pharmaceutical segment delivered Adjusted Segment Operating Profit growth of 9%.
Prescription Technology Solutions Segment

First-quarter revenues were $1.1 billion, an increase of 21%, driven by our biopharma services programs due to prescription volume growth, and third-party logistics and technology service revenues.
First-quarter Segment Operating Profit was $144 million. Adjusted Segment Operating Profit was $165 million, an increase of 19%, driven by growth from access, affordability, and adherence solutions.
Medical-Surgical Solutions Segment

First-quarter revenues were $2.6 billion, an increase of 3%, driven by growth in the primary care business, partially offset by lower sales of COVID-19 tests and lower contribution from kitting, storage, and distribution of ancillary supplies for the U.S. government’s COVID-19 vaccine program.
First-quarter Segment Operating Profit was $256 million. Adjusted Segment Operating Profit was $268 million, an increase of 4%, driven by organic business performance as well as growth and improvements in the primary care business.
International Segment

First-quarter revenues were $6.5 billion. On an FX-Adjusted basis, revenues were $7.1 billion, a decrease of 23%, driven by the divestitures of McKesson’s UK and Austrian businesses.
First-quarter Segment Operating Loss was $6 million. On an FX-Adjusted basis, Adjusted Segment Operating Profit was $152 million, a decrease of 11%, driven by the divestitures of McKesson’s Austrian and UK businesses, partially offset by the reduction of depreciation and amortization on European assets under agreements to sell.
Opioid-Related Litigation

McKesson has settled, or reached agreements to settle, the opioid-related claims of all 50 states, as well as the District of Columbia and all eligible territories.
On May 3, 2022, McKesson reached an agreement in principle with the State of Washington.
On June 27, 2022, McKesson reached an agreement in principle with the State of Oklahoma.
On July 4, 2022, after a full trial, a federal judge ruled that McKesson along with two other distributors could not be held liable to two West Virginia subdivisions for contributing to the opioid crisis.
Corporate Responsibility Updates

McKesson was recognized by Forbes as one of the "Best Employers for Women," achieving an industry-leading ranking and demonstrating its outstanding progress in promoting gender equity and diversity in the workplace.
For the seventh consecutive year, McKesson was named a "Best Place to Work for Disability Inclusion." McKesson earned a top-ranking score of 100 on the 2022 Disability Equality Index, a joint initiative of the American Association of People with Disabilities and Disability:IN.
Fiscal 2023 Outlook

McKesson raised fiscal 2023 Adjusted Earnings per Diluted Share guidance to $23.95 to $24.65 from the previous range of $22.90 to $23.60 to reflect first-quarter operating performance and increased contribution from the U.S. government’s COVID-19 vaccine distribution, kitting, and storage programs and COVID-19 tests.

Fiscal 2023 Adjusted Earnings per Diluted Share guidance includes approximately $0.99 to $1.29 of impacts attributable to the following:

Fiscal 2023 Adjusted Earnings per Diluted Share guidance, excluding the impacts of the above items from both fiscal 2023 guidance and fiscal 2022 results, indicates 10% to 15% forecasted growth compared to prior year.

Additional modeling considerations will be provided in the earnings call presentation.

Conference Call Details

McKesson has scheduled a conference call for today, Wednesday, August 3rd at 4:30 PM ET to discuss the company’s financial results. The audio webcast of the conference call will be available live and archived on McKesson’s Investor Relations website at investor.mckesson.com.

Upcoming Investor Events

McKesson management will be participating in the following investor conference:

Morgan Stanley Healthcare Conference, September 13, 2022
Audio webcast, and a complete listing of upcoming events for the investment community, including details and updates, will be available on McKesson’s Investor Relations website.

Non-GAAP Financial Measures

GAAP refers to the U.S. generally accepted accounting principles. This press release includes GAAP financial measures as well as Non-GAAP financial measures, including Adjusted Gross Profit, Adjusted Operating Expenses, Adjusted Other Income, Adjusted Income Tax Expense, Adjusted Earnings, Adjusted Earnings per Diluted Share, Adjusted Segment Operating Profit, Adjusted Segment Operating Profit Margin, Adjusted Corporate Expenses, Adjusted Operating Profit, FX-Adjusted results and Free Cash Flow which are financial measures not calculated in accordance with GAAP. Refer to the "Supplemental Non-GAAP Financial Information" section of the accompanying financial statement tables for the definitions and usefulness of the Company’s Non-GAAP financial measures and the attached schedules for reconciliations of the differences between the Non-GAAP financial measures and their most directly comparable GAAP financial measures.

The Company does not provide forward-looking guidance on a GAAP basis as McKesson is unable to provide a quantitative reconciliation of this forward-looking Non-GAAP measure to the most directly comparable forward-looking GAAP measure, without unreasonable effort, because McKesson cannot reliably forecast LIFO inventory-related adjustments, certain litigation loss and gain contingencies, restructuring, impairment and related charges, and other adjustments, which are difficult to predict and estimate. These items are inherently uncertain and depend on various factors, many of which are beyond the company’s control, and as such, any associated estimate and its impact on GAAP performance could vary materially.

Novel Costimulatory Bispecific Antibody Shows Encouraging Anti-tumor Activity When Combined with PD-1 Inhibitor Libtayo® (cemiplimab) in Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)

On August 3, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that encouraging initial data from an ongoing Phase 1/2 trial investigating REGN5678, a novel PSMAxCD28 costimulatory bispecific antibody, in combination with the company’s PD-1 inhibitor Libtayo (cemiplimab) in advanced metastatic castration-resistant prostate cancer (mCRPC) (Press release, Regeneron, AUG 3, 2022, View Source [SID1234617339]). REGN5678 is one of Regeneron’s three clinical-stage costimulatory bispecifics, all of which are designed to bridge T cells to cancer cells and augment CD28 signaling to increase anti-tumor activity in combination with Libtayo or a CD3 bispecific.

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"In past clinical trials, metastatic castration-resistant prostate cancer has been largely unresponsive to PD-1 inhibition and immunotherapy in general, leaving patients with inadequate treatment options, a poor prognosis and an expected survival of one to two years depending on the treatment history," said Mark Stein, M.D., a trial investigator and Associate Professor of Medical Oncology at Columbia University Vagelos College of Physicians and Surgeons. "These initial data provide the first clinical evidence indicating that a costimulatory bispecific antibody may synergistically combine with an anti-PD-1 agent such as Libtayo to enable activity against a tumor class previously resistant to anti-PD-1 immunotherapy. We look forward to further investigating the safety and efficacy of this combination."

The Phase 1/2, first-in-human, open label trial is currently enrolling patients with advanced mCRPC whose tumors have previously progressed on multiple anti-androgen therapies, with a majority also having received prior chemotherapy. In the Phase 1 dose-escalation portion, patients are initiated with weekly doses of REGN5678, for three weeks, to assess the safety and efficacy of this novel costimulatory antibody alone, which then continues in combination with standard dose Libtayo. The primary endpoints are safety, tolerability and pharmacokinetics. The key secondary endpoint is objective response rate defined as a ≥50% decline of prostate-specific antigen (PSA) from baseline and/or tumor shrinkage. PSA is a protein produced by the prostate gland and is commonly used as a biomarker to diagnose and follow prostate cancer, as many mCRPC patients have disease limited to bone lesions and cannot be assessed by conventional RECIST 1.1 criteria.

Preliminary data from the ongoing dose-escalation portion of the trial, across 8 dose level cohorts and a total of 33 patients, showed dose-dependent anti-tumor activity per centrally collected PSA values, as well as investigator reports. Not all patients have undergone or completed tumor assessments and the data are not yet final. At the lowest dose levels (cohorts 1-5), there was almost no evidence of anti-tumor activity, with only 1 of 17 patients showing a decrease (22%) in PSA; there were no ≥grade (Gr) 3 immune-related adverse events (irAE) at these doses. The lack of anti-tumor activity among these patients was consistent with the approximate 6% response rate reported in other trials with anti-PD1 monotherapy.

At the next three dose levels (cohorts 6-8), evidence of dose-dependent anti-tumor activity was generally seen within 6 weeks of starting combination treatment as follows:

Cohort 6: 1 of 4 patients experienced a 100% decrease in PSA and a complete response (CR) in target lesions based on RECIST 1.1 criteria. The patient discontinued therapy due to a Gr3 irAE of the skin (that was considered to be a recurrence of a pre-existing condition, and has resolved with treatment per investigator report). The patient has maintained the 100% decrease in PSA and CR in target lesions for approximately 10 months to date per investigator report.
Cohort 7: 3 of 8 patients experienced decreases in PSA of >99%, 44% and 22%. Two of these three patients had a Gr3 AE (aseptic encephalitis and seizure, respectively, both of which have resolved).
Cohort 8: 3 of 4 patients experienced decreases in PSA of >99%, >99% and 82%. Of the two patients with >99% PSA reductions, one experienced a Gr3 case of mucositis (resolved) and the other experienced a Gr3 case of acute inflammatory demyelinating polyradiculopathy (ongoing).
In terms of safety, no ≥Gr3 irAEs were observed in patients without anti-tumor activity, and the occurrence of irAEs was correlated with anti-tumor activity; this is consistent with previous trials with anti-PD-1 immunotherapy, wherein irAEs have been reported to occur at a higher rate in responding patients. No Gr4 irAEs or ≥Gr2 cytokine release syndrome have been observed in the trial to date. There was one death that was considered unrelated to treatment. In this trial, irAEs are being treated according to standard management practices used for checkpoint inhibitors.

Additional data are planned for presentation at an upcoming medical meeting.

"Through extensive preclinical research, we hypothesized that augmenting T-cell costimulation alongside PD-1 inhibition could be a key to turning immunologically ‘cold’ tumors ‘hot’," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "These preliminary data for our PSMAxCD28 costimulatory bispecific provide the first clinical evidence supporting the promise of our broader pipeline of costimulatory bispecifics in diverse solid tumors and hematological malignancies. By combining these costimulatory bispecifics with Libtayo or our CD3 bispecifics, we have the opportunity to create novel therapeutic synergies to address some of the most difficult-to-treat cancers. We look forward to partnering with the oncology community on this ambitious and potentially groundbreaking research."

The combination of REGN5678 and Libtayo is currently under clinical development for mCRPC, and its safety and efficacy have not been fully evaluated by any regulatory authority.

Nuvalent to Present at the Canaccord Genuity 42nd Annual Growth Conference

On August 3, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported that James Porter, Ph.D., Chief Executive Officer, will present at the Canaccord Genuity 42nd Annual Growth Conference on Wednesday, August 10, 2022, at 4:00 p.m. ET in Boston (Press release, Nuvalent, AUG 3, 2022, View Source [SID1234617385]).

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