On February 5, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the fourth quarter and full year 2020 and provided a business update (Press release, Regeneron, FEB 5, 2021, View Source [SID1234574688]).

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"In 2020, the Regeneron team rapidly mobilized our significant scientific, development, manufacturing, and operational capabilities to bring our monoclonal antibody cocktail, REGEN-COV, to patients with COVID-19 through an Emergency Use Authorization," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "In 2021, in addition to our ongoing work on COVID-19, we expect further diversified growth driven by continued EYLEA momentum, expanded approvals and increased market penetration for Dupixent, and new launches for Libtayo in oncology. We anticipate U.S. regulatory action for Libtayo in both non-small cell lung cancer and basal cell carcinoma within the next month – and anticipate additional readouts later this year from across our oncology pipeline, including the bispecific platform."

Financial Highlights

"In 2020, Regeneron delivered double-digit top- and bottom-line growth and significant shareholder value despite the unprecedented circumstances of a global pandemic," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "As we look ahead into 2021 and beyond, our business momentum and strong balance sheet give us confidence as we invest in R&D for long-term growth and execute on our capital allocation priorities."

Business Highlights

Key Pipeline Progress
Regeneron has approximately 30 product candidates in clinical development, including five marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

Dupixent (dupilumab)

In November 2020, the European Commission (EC) extended the marketing authorization in the European Union (EU) to include children 6 to 11 years of age with severe atopic dermatitis who are candidates for systemic therapy.
In October 2020, the Company and Sanofi announced that a Phase 3 trial met its primary and all key secondary endpoints in children aged 6 to 11 years with uncontrolled moderate-to-severe asthma. A supplemental Biologics License Application (sBLA) was subsequently submitted and a submission in the EU is planned by the end of the first quarter of 2021.
Phase 3 studies in chronic inducible urticaria, chronic sinusitis without nasal polyposis, and allergic fungal rhinosinusitis were initiated.
REGEN-COV (casirivimab and imdevimab), a dual antibody cocktail to SARS-CoV-2 virus

In November 2020, REGEN-COV received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). REGEN-COV is authorized for the treatment of mild to moderate COVID-19 in certain patients at high risk for progressing to severe COVID-19 and/or hospitalization.
In January 2021, the Company announced a second agreement with the U.S. government to manufacture and deliver REGEN-COV. The U.S. government has agreed to acquire up to 1.25 million additional doses at the lowest treatment dose authorized or approved by the FDA for the indication authorized under the EUA, resulting in payments to the Company of up to $2.625 billion in the aggregate. The U.S. government is obligated to purchase all filled and finished doses of drug product delivered by June 30, 2021, and may accept doses through September 30, 2021 at its discretion. A number of factors may impact available filled and finished supply by June 30, 2021, including manufacturing considerations and authorized dose levels. The agreement is in addition to the July 2020 agreement with the U.S. government for approximately 300,000 doses.
In February 2021, the European Medicines Agency (EMA) announced it had commenced a Rolling Review of data for the casirivimab and imdevimab antibody cocktail. Data on the safety, tolerability, and efficacy of the antibody cocktail will be shared with the EMA as they become available in the coming months.
In October 2020, the Company announced additional positive results from an ongoing Phase 2/3 seamless trial in the COVID-19 outpatient setting showing that REGEN-COV significantly reduced viral load and COVID-19 medical visits (hospitalizations, emergency room, urgent care visits, and/or physician office/telemedicine visits). Initial clinical data from this trial were published in the New England Journal of Medicine (NEJM) in December 2020.
A Phase 2 dose-ranging treatment study in non-hospitalized patients with COVID-19 was initiated and a lower 1,200 mg dose is being evaluated in the ongoing outpatient trial.
In December 2020, the Company announced initial encouraging data from an ongoing Phase 1/2/3 trial in seronegative hospitalized COVID-19 patients requiring low-flow oxygen. The Phase 3 program in hospitalized patients will continue based on passing a futility analysis evaluating the risk of death or receiving mechanical ventilation and demonstrating positive reductions in viral load. In October 2020, the Independent Data Monitoring Committee (IDMC) for this trial recommended that, based on a potential safety signal and an unfavorable risk/benefit profile at this time, further enrollment of patients requiring high-flow oxygen or mechanical ventilation be placed on hold.
The United Kingdom-based RECOVERY trial continues to evaluate REGEN-COV in hospitalized patients and has enrolled more than 6,000 patients in the cohort randomizing patients 1:1 to receive REGEN-COV or placebo.
In January 2021, the Company announced positive initial results from an ongoing Phase 3 trial evaluating REGEN-COV used as a passive vaccine for the prevention of COVID-19 in people at high risk of infection (due to household exposure to a COVID-19 patient). An exploratory analysis was conducted on the first approximately 400 evaluable individuals enrolled in the trial, who were randomized to receive passive vaccination with REGEN-COV (1,200 mg via subcutaneous injections) or placebo.
In January 2021, the Company announced that preclinical studies showed that the REGEN-COV antibody cocktail retains its potent neutralizing ability against circulating SARS-CoV-2 variants identified in the United Kingdom, South Africa, and Brazil. Both antibodies in the cocktail retained their potency against the UK variant (B.1.1.7); imdevimab retained its potency against the South African variant (B.1.351), while casirivimab potency was reduced but still comparable to that of other single antibodies in development against the original virus. The REGEN-COV antibody cocktail was prospectively designed so that if variants arose affecting one component, the other component could compensate and still allow for potent neutralizing activity. In fact, as reported in Science in June 2020, Regeneron scientists predicted the key mutation that has since appeared in the South African and Brazil variants, and further showed that this mutation would lower potency of the casirivimab component, but be compensated for by the imdevimab component.
Libtayo (cemiplimab)

The FDA accepted for priority review, with a target action date of February 28, 2021, the sBLA for Libtayo as monotherapy to treat patients with first-line locally advanced or metastatic non-small cell lung cancer (NSCLC) with ≥50% PD-L1 expression. A regulatory application for Libtayo as monotherapy in first-line NSCLC was also submitted in the EU.
The FDA accepted for priority review, with a target action date of March 3, 2021, the sBLA for Libtayo for the treatment of patients with locally advanced or metastatic basal cell carcinoma (BCC). A regulatory application for Libtayo in advanced BCC was also submitted in the EU.
Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn)

In October 2020, the FDA approved Inmazeb (REGN-EB3) for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including newborns of mothers who have tested positive for the infection.
REGN5458, a bispecific antibody targeting BCMA and CD3

In December 2020, the Company announced updated data from the Phase 1 portion of a Phase 1/2 trial in patients with relapsed or refractory (R/R) multiple myeloma. The results continued to show deep and durable responses in patients with heavily-pretreated multiple myeloma and were shared in an oral presentation at the virtual 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.
Odronextamab, a CD20xCD3 bispecific antibody

In December 2020, updated results from the Phase 1 trial in R/R follicular lymphoma, diffuse large B-cell lymphoma, and other B-cell non-Hodgkin lymphomas were shared in an oral presentation at ASH (Free ASH Whitepaper) and included patient follow-up data of up to 3 years.
In December 2020, the Company announced it was pausing new enrollment of patients with B-cell non-Hodgkin lymphomas (B-NHL) in its trials in compliance with an FDA partial clinical hold. The FDA requested that the Company amend the trial protocols in order to further reduce the incidence of ≥Grade 3 cytokine release syndrome (CRS) during step-up dosing. The Company is working with the FDA to amend the protocol, with the goal of resuming patient enrollment within the first half of 2021.
Additional Bispecific Antibodies

In addition to REGN5458 and odronextamab, the Company has advanced two CD3 bispecifics into clinical trials including MUC16xCD3 (REGN4018), which is being studied in ovarian cancer.
Three costimulatory CD28 bispecifics are now in clinical trials targeting prostate cancer, ovarian cancer, and other solid tumors.
Also in clinical development is the first of a third class of bispecifics, METxMET (REGN5093), in non-small cell lung cancer driven by MET mutations and/or amplifications.
Itepekimab, an antibody to IL-33

The Company and Sanofi have initiated a Phase 3 program in chronic obstructive pulmonary disease (COPD).
REGN5713-5714-5715, a multi-antibody therapy to Betv1

A Phase 3 study in birch allergy was recently initiated. REGN5713-5714-5715 is designed to treat allergic inflammatory conditions caused by the allergen Betv1, which is the main allergen responsible for birch pollen allergies. Birch pollen allergy is one of the most common causes of seasonal allergies that occur in the spring, and is also believed to trigger "oral allergy syndrome" food reactions to related allergens found in fruits and nuts such as apples, pears, and cherries.
Select 2021 Milestones

Programs

Milestones

EYLEA

–

Report results from Phase 2 study for high-dose formulation in neovascular age-related macular degeneration (wet AMD)

Dupixent

–

FDA decision on sBLA and MAA submission for asthma in pediatrics (6–11 years of age)

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Report results from Part B of the Phase 3 study in adults and adolescents with eosinophilic esophagitis (EoE)

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Report results from Phase 3 study in prurigo nodularis

REGEN-COV (casirivimab and imdevimab)

–

Report additonal data from Phase 3 portion of COVID-19 study in non-hospitalized patients

–

Report results for lower 1,200 mg dose in Phase 3 portion of COVID-19 study in non-hospitalized patients

–

Report additional data from Phase 3 portion of COVID-19 prevention study in household contacts

–

Data to be reported from Phase 3 United Kingdom-based RECOVERY trial in hospitalized patients

–

Report data from Phase 2 dose-ranging virology study in non-hospitalized patients

–

Submit BLA and MAA for COVID-19

Libtayo

–

FDA decision on sBLA (target action date of February 28, 2021) and EC decision on regulatory submission for first-line NSCLC, monotherapy

–

Interim analysis from Phase 3 study in first-line NSCLC, chemotherapy combination

–

FDA decision on sBLA (target action date of March 3, 2021) and EC decision on regulatory submission for advanced BCC

–

Interim analysis from Phase 3 study in cervical cancer

REGN5458 (BCMA and CD3 Bispecific Antibody)

–

Complete patient enrollment in potentially pivotal Phase 2 study in multiple myeloma

–

Initiate pivotal trials in earlier lines of multiple myeloma therapy

Odronextamab (CD20 and CD3 Bispecific Antibody)

–

Complete patient enrollment in potentially pivotal Phase 2 study in B-NHL

–

Initiate Phase 3 program

Praluent

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FDA decision on sBLA for homozygous familial hypercholesterolemia (HoFH) in adults (target action date of April 4, 2021)

Evkeeza (evinacumab) (ANGPTL3 Antibody)

–

FDA decision on BLA (target action date of February 11, 2021) and EC decision on MAA for HoFH

Fasinumab (NGF Antibody)

–

Report additional longer-term safety results from Phase 3 studies in osteoarthritis pain of the knee or hip

–

Continue discussions with regulatory authorities and determine next steps for the program

Fourth Quarter and Full Year 2020 Financial Results

Effective January 1, 2020, Regeneron implemented changes in the presentation of its financial statements related to certain reimbursements and other payments for products developed and commercialized with collaborators. The Company made these changes in presentation to better reflect the nature of the Company’s costs incurred and revenues earned pursuant to arrangements with collaborators and to enhance the comparability of Regeneron’s financial statements with industry peers. The change in presentation has been applied retrospectively. See note (4) below for further information.

Revenues

Total revenues increased by 30% to $2.423 billion in the fourth quarter of 2020, compared to $1.864 billion in the fourth quarter of 2019. Full year 2020 total revenues increased 30% to $8.497 billion, compared to $6.558 billion for the full year 2019.

EYLEA net product sales in the United States increased to $1.343 billion in the fourth quarter of 2020, compared to $1.222 billion in the fourth quarter of 2019. Full year 2020 EYLEA net product sales in the United States increased to $4.947 billion, compared to $4.644 billion for the full year 2019. Overall distributor inventory levels for EYLEA in the United States remained within the Company’s one-to-two-week targeted range.

Net product sales of REGEN-COV were $146 million in the fourth quarter of 2020 and $186 million for the full year of 2020.

Total revenues also include Sanofi and Bayer collaboration revenues(2) of $678 million in the fourth quarter and $2.373 billion for the full year 2020, compared to $482 million in the fourth quarter and $1.549 billion for the full year 2019. Sanofi collaboration revenue increased primarily due to the Company’s share of profits from commercialization of antibodies, which were $230 million and $785 million in the fourth quarter and full year 2020, respectively, compared to $104 million and $209 million in the fourth quarter and full year 2019, respectively. The change in the Company’s share of profits from commercialization of antibodies was primarily driven by higher Dupixent profits. In addition, in the third quarter of 2020, the Company earned the first $50 million sales-based milestone from Sanofi, upon annual sales of antibodies outside the United States exceeding $1.0 billion on a rolling twelve-month basis.

Refer to Table 4 for a summary of collaboration revenue.

Other revenues in the fourth quarter and full year of 2020, compared to the same periods in the prior year, increased primarily due to recognition of revenue of $43 million and $187 million, respectively, in connection with the Company’s agreement with the Biomedical Advanced Research Development Authority (BARDA) related to funding of certain development activities for antibodies related to the treatment of COVID-19. Other revenues for the full year of 2020 also increased due to recognition of revenue in connection with the Company’s agreement with BARDA related to funding of certain Inmazeb development activities and Sanofi’s reimbursement for manufacturing commercial supplies of Praluent.

Operating Expenses

The higher GAAP and non-GAAP R&D expenses in the fourth quarter and full year 2020, compared to the same periods in the prior year, were primarily due to additional costs incurred in connection with COVID-19 related development activities. The higher GAAP and non-GAAP R&D expenses for full year 2020 were also due to additional costs incurred in connection with the Company’s earlier-stage pipeline, higher headcount and headcount-related costs, and an increase in clinical manufacturing activities. GAAP R&D expenses for full year 2020 included $85 million of up-front payments in connection with the Intellia collaboration agreement, and GAAP R&D expenses for full year 2019 included a $400 million up-front payment in connection with the Alnylam collaboration agreement.
The change in GAAP and non-GAAP SG&A expenses in the fourth quarter and full year 2020, compared to the same periods in the prior year, was primarily due to an increase in commercialization-related costs for EYLEA and Libtayo, higher headcount-related costs, and, effective April 1, 2020, no longer receiving Praluent-related cost reimbursements from Sanofi for Regeneron-incurred expenses. GAAP SG&A expenses for the fourth quarter and full year 2020 were also positively impacted by a reversal of $121 million in accruals for litigation-related loss contingencies in the fourth quarter of 2020 as a result of the October 2020 ruling by the Technical Board of Appeal of the European Patent Office and its impact on certain patent infringement actions in Europe relating to Praluent. In addition, in the fourth quarter of 2019, the Company recorded a $35 million GAAP SG&A charge related to employee separation costs, as the Company eliminated certain commercialization activities and related headcount in connection with the restructuring of the antibody agreement with Sanofi.
The increase in COGS in the fourth quarter and full year 2020, compared to the same periods in the prior year, was primarily due to the recognition of manufacturing costs in connection with the initiation of product sales of REGEN-COV (which commenced in the third quarter of 2020) and Praluent in the United States (which were recorded by Sanofi prior to April 1, 2020), as well as higher product sales of Libtayo and EYLEA in the United States. These increases were partly offset by lower period costs for the Company’s Limerick commercial manufacturing facility and lower inventory write-downs and reserves.
The increase in COCM in the fourth quarter and full year 2020, compared to the same periods in the prior year, was primarily due to the recognition of manufacturing costs associated with Dupixent and recognition of costs in connection with manufacturing ex-U.S. commercial supplies of Praluent for Sanofi. In addition, COCM increased for full year 2020 due to process validation costs in connection with manufacturing Inmazeb under our BARDA agreement.
Other operating (income) expense, net, includes recognition of a portion of amounts previously deferred in connection with up-front and development milestone payments, as applicable, received in connection with the Company’s collaborative arrangements. The increase in other operating income in the fourth quarter and full year 2020 was primarily due to the recognition of cumulative catch-up adjustments of $100 million, net, arising from an update to the estimate of the stage of completion for certain collaboration programs.
Other Financial Information

GAAP other income (expense), net, includes the recognition of net gains on equity securities of $60 million in the fourth quarter and $222 million for the full year 2020, compared to net gains of $189 million in the fourth quarter and $118 million for the full year 2019. In August 2020, the Company issued and sold $1.250 billion aggregate principal amount of 1.750% senior unsecured notes due 2030 and $750 million aggregate principal amount of 2.800% senior unsecured notes due 2050, for which the associated interest expense is included in GAAP and non-GAAP other income (expense), net.

GAAP income tax expense was $75 million and the effective tax rate was 6.2% in the fourth quarter of 2020, compared to $98 million and 11.0% in the fourth quarter of 2019. GAAP income tax expense was $297 million and the effective tax rate was 7.8% for the full year 2020, compared to $313 million and 12.9% for the full year 2019. The GAAP effective tax rate for the fourth quarter and full year 2020 was positively impacted, compared to the U.S. federal statutory rate, primarily by stock-based compensation, federal tax credits for research activities, and income earned in foreign jurisdictions with tax rates lower than the U.S. federal statutory rate. In the fourth quarter and full year 2020, the non-GAAP effective tax rate was 7.7% and 9.1%, respectively, compared to 10.6% and 14.6% in the fourth quarter and full year 2019, respectively.

GAAP net income per diluted share was $10.24 in the fourth quarter of 2020, compared to GAAP net income per diluted share of $6.93 in the fourth quarter of 2019. GAAP net income per diluted share was $30.52 for the full year 2020, compared to GAAP net income per diluted share of $18.46 for full year 2019. Non-GAAP net income per diluted share was $9.53 in the fourth quarter of 2020, compared to non-GAAP net income per diluted share of $7.50 in the fourth quarter of 2019. Non-GAAP net income per diluted share was $31.47 for the full year 2020, compared to non-GAAP net income per diluted share of $24.67 for the full year 2019. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

During 2020, the Company repurchased 1.6 million shares of its common stock under the Company’s share repurchase program. As of December 31, 2020, the Company had repurchased the entire $1.0 billion it was authorized to repurchase under the program.

In January 2021, the Company’s board of directors authorized a new share repurchase program to repurchase up to $1.5 billion of the Company’s common stock. Repurchases may be made from time to time at management’s discretion through a variety of methods. The program has no time limit and can be discontinued at any time.

Net cash provided by operating activities in the fourth quarter of 2020 was $1.231 billion, compared to $787 million in the fourth quarter of 2019, resulting in $1.070 billion in free cash flow for the fourth quarter of 2020, compared to $648 million for the fourth quarter of 2019. Net cash provided by operating activities for the full year 2020 was $2.618 billion, compared to $2.430 billion in net cash provided by operating activities for the full year 2019, resulting in $2.004 billion in free cash flow for the full year 2020, compared to $2.000 billion for the full year 2019.

2021 Financial Guidance(3)

The Company’s full year 2021 financial guidance consists of the following components:

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its fourth quarter and full year 2020 financial and operating results on Friday, February 5, 2021, at 8:30 AM. To access this call, dial (888) 660-6127 (U.S.) or (973) 890-8355 (International), conference ID 1580376. A link to the webcast may be accessed from the "Investors and Media" page of Regeneron’s website at www.regeneron.com. A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days.

On February 5, 2021 Bolt Biotherapeutics reported that it has raked in $230 million from its upsized IPO (Press release, Bolt Biotherapeutics, FEB 5, 2021, View Source [SID1234574707]).

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One of the first immune-stimulating cancer drugs, prostate cancer vaccine Provenge, never quite lived up to expectations, but the scientist whose work led to the development of the product remains committed to immuno-oncology.

He’s Edgar Engleman, M.D., professor of medicine and pathology at Stanford University. His creation, Bolt Biotherapeutics, founded in 2015, recently launched its first clinical trial of its lead compound, which is part of a new class of cancer drugs called immune-stimulating antibody conjugates (ISACs). The drug is a tumor-targeting antibody that’s connected to an agent that stimulates the immune system.

In animal studies, the drug, which targets the tumor marker HER2, eradicated large tumors, according to a presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in Maryland back in 2019. The drug also protected the animals from the development of new tumors, the company said.

That candidate, known as BDC-1001, is now in the clinic as a treatment of patients with HER2-expressing solid tumors, including those with HER2-low tumors. Bolt’s approach is different from a typical antibody-drug conjugate method of action, because its ISAC technology is based around the idea of connecting antibodies to agents that stimulate the immune system to attack the cancer rather than to compounds that directly poison cancer cells. And it’s designed to be able to be used as a solo therapy.

"We have designed BDC-1001 as a Boltbody ISAC comprised of a HER2-targeting biosimilar trastuzumab conjugated to one of our proprietary TLR7/8 agonists to maximize the potential anti-tumor response," the biotech said in its recent SEC-1 filing.

It started a phase 1/2 trial of BDC-1001 around a year ago and is currently in the dose-escalation portion of the trial; it expects to advance into phase 2 dose expansions in 2021 in "four clinically important and commercially compelling indications," it said.

"As of January 12, 2021, we have treated 19 patients and BDC-1001 appears to be well tolerated with mild to moderate adverse events and no dose-limiting toxicities, or DLTs, or drug-related serious adverse events observed to date. We have seen clinical activity in the form of stable disease, reductions in tumor volume and increases in pharmacodynamic markers that we believe are consistent with our proposed mechanism of action."

Bolt also has other, earlier preclinical programs, including one that focuses on CEA, a well-known tumor antigen that is overexpressed in various solid tumors with significant unmet medical need including, but not limited to, colorectal cancer, non-small cell lung cancer, pancreatic cancer and breast cancer. That could be in the clinic by next year.

It’s also at work on another early program for a PD-L1 Boltbody ISAC, which is targeting patients with tumors that are nonresponsive or become refractory to immune checkpoint blockade.

The biotech will trade on the Nasdaq under the ticker "BOLT." The company previously filed for a $150 million IPO but, like so many in the past year, went well past this.

On February 5, 2021 Bristol Myers Squibb (NYSE: BMY) reported that the company will take part in a fireside chat at Guggenheim’s Virtual Healthcare Talks | 2021 Oncology Day, which will be webcast on Friday, February 12, 2021 (Press release, Bristol-Myers Squibb, FEB 5, 2021, View Source;2021-Oncology-Day/default.aspx [SID1234574672]). Chris Boerner, Ph.D., Executive Vice President, Chief Commercial Officer will answer questions about the company at 12 p.m. ET.

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Investors and the general public are invited to listen to a live webcast of the session at View Source Material related to the company’s presentation will be available at the same website at the start of the live webcast. An archived edition of the session will be available later that day.

On February 5, 2021 Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built proteins known as DARPin therapeutics, reported its unaudited financial results for 2020 and corporate highlights for the fourth quarter of 2020 (Press release, Molecular Partners, FEB 5, 2021, View Source,CHF%2062.8%20million%20in%202020 [SID1234574689]).

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"In 2020, our pipeline grew and evolved in several key ways, including clinical proof of biological activity for our first localized immune agonist program, important platform advances for the design of new immunomodulatory DARPin candidates, and of course the rapid progression to the clinic of our COVID-19 program, specifically designed to deliver differentiated therapeutics that answer the need of an evolving global viral pandemic," said Patrick Amstutz, Ph.D., chief executive officer of Molecular Partners. "We have significantly expanded the horizons of possibility for DARPin molecules in 2020, and look forward to executing on multiple parallel clinical programs with very diverse targets in the year ahead."

Antiviral program: Rapid development progress for highly differentiated anti-COVID-19 multi-DARPin candidates with unique advantages
In October 2020, the Company announced further supportive preclinical data from in vivo assessments of its two DARPin candidates targeting SARS-CoV-2. These candidates showed robust activity in an aggressive viral challenge hamster model, supporting potential efficacy as therapeutic options in patients with late-stage disease. In a highly susceptible COVID-19 challenge model developed by expert virologists at Freie Universität Berlin, hamsters were first infected with SARS-CoV-2 and then administered either select doses of anti-COVID-19 DARPin candidates or placebo, at either 0, 6, or 24 hours. In the five-day experiment, all animals treated with DARPin molecules recovered and survived, while 83% of animals in the placebo group had to be euthanized due to severe disease progression.

Further in October, the Company signed a collaboration with Novartis for the co-development of ensovibep and MP0423 as well as options for global commercialization. This collaboration combines the innovative protein drug development expertise of Molecular Partners with Novartis’ expertise in clinical development, manufacturing, regulatory affairs & commercialization to accelerate global development of both candidates.

Under the terms of the collaboration agreement, Molecular Partners received a cash payment of CHF 20 million (~$22 million USD). As part of the transaction, Novartis also agreed to acquire CHF 40 million (~$44 million USD) worth of ordinary shares at a price of CHF 23 (~$25 USD) per share. As a result, Novartis now holds approximately 6% of the outstanding shares of Molecular Partners. Molecular Partners is eligible to receive a future milestone payment of CHF 150 million (~$165 million USD), upon Novartis exercising the option to both therapeutic candidates, additional clinical milestones of CHF 5 million associated with MP0423, and 22% royalty on sales in commercial countries. Molecular Partners has agreed to forgo royalties in lower income countries, and is aligned with Novartis’ plans to ensure affordability based on countries’ needs and capabilities.

In November 2020, the Company dosed the first cohort of healthy volunteers in a Phase 1, randomized, double-blind, placebo-controlled, first-in-human single ascending dose study to evaluate the safety, tolerability, and pharmacokinetics of intravenously administered ensovibep in up to 24 healthy volunteers divided into three dose cohorts, with each cohort stratified 3:1 in favor of ensovibep. We expect to report initial data in Q1 2021. Multiple characteristics of DARPin therapeutics make them ideally suited for antiviral therapies, particularly at time of global need. They also offer logistical advantages that other potential therapeutics in development may not possess, including (i) sub-picomolar potency, allowing investigation of subcutaneous administration as both early intervention and potential prophylaxis; (ii) highly scalable microbial manufacturing, allowing for up to 4 production runs on the same fermenter, per month; and (iii) high temperature stability (>80°C) which may allow for avoidance of cumbersome cold chain storage. Molecular Partners is actively exploring opportunities to develop DARPin therapeutics against other viral infections with significant unmet global need.

Another important characteristic of DARPin molecules as a class, and specifically against SARS-CoV-2, is the advantage of cooperative binding: multiple DARPin domains, bound to each other on a single chain, collaboratively interacting with the target protein. In the example of SARS-CoV-2, this cooperative binding allows for much stronger target engagement and inhibition. Moreover, with the rise of new mutations and viral variants, cooperative binding allows DARPin candidates to maintain a high level of potency even if one or two of the three binding domains lose some of their individual binding strength. As described in recent results, ensovibep and MP0423 continue to inhibit SARS-CoV-2 infections in vitro in the presence of multiple mutations, including those present in the B.1.1.7 P.1 and B.1.351 variants, first identified in UK, Brazil and SA, respectively.

Oncology: Clinical biomarkers provide support for MP0310/AMG 506 (targeting FAP x 4-1BB)
Initial clinical data from the ongoing phase 1 dose escalation study of MP0310 were presented in December 2020 at the Company’s virtual R&D day and support preclinical observations. At the time of analysis, 19 of the 22 patients were available for evaluation. Of these, 50% of patients achieved stable disease (SD). To date, this study has reported no dose-limiting toxicities and no serious adverse events (SAEs) of special interest. Tumor biopsies show tumor-localized immune response consistent with the predicted MoA of MP0310. The PK profile appears to be dose dependent additional dosing regimens are currently being explored.

Additionally, biopsy data showed significant increases in activation across multiple immune cell types, while inflammatory markers in the peripheral blood were unchanged. Grade 2/3 infusion-related responses (IRRs) were observed in 12 patients and were manageable.

Oncology: Preclinical data supports mechanism of MP0317 (targeting FAP x CD40)
In 2020, the Company presented preclinical data at research conferences strongly supporting the intended profile and CD40-mediated immune activation capabilities of MP0317. In a mouse model, a mouse-specific version of MP0317 was found to substantially inhibit the progression of FAP-positive tumors without showing any of the toxicities seen with administration of a mouse CD40 antibody. Phase 1 initiation for MP0317 is now anticipated in H2 2021 due to a loss of drug supply associated with fill/finish procedures. New batches of MP0317 will be produced in H1 2021 and the clinical study is anticipated to initiate shortly thereafter.

Oncology: Novel therapeutic platforms address key challenges facing non-DARPin approaches
At its virtual R&D Day in December 2020, the Company shared data demonstrating the substantial progress made across the CD3/T cell engager and peptide MHC (pMHC) therapeutics platforms, which both open an array of new opportunities for modulating the immune system to fight disease.

CD3/T cell engagers: The CD3/T cell engager therapeutics platform is designed to avoid the dose-limiting toxicities that T cell engagers have generally produced to-date. The Company has now demonstrated both highly selective T cell activation in the tumor microenvironment, as well as the capacity for ‘slow release’ activation of T cells in the circulation, giving multiple levels of control over this key immuno-oncologic mechanism to help reduce off-tumor effects, achieve higher dose levels and ultimately enhanced clinical benefit. The multi-domain DARPin format potentially allows a high level of functional ‘tuning’ to a target indication. In models of acute myeloid leukemia, multi-DARPin CD3/T cell engager research candidates have demonstrated high potency, improved selectivity and lower levels of inflammatory cytokine stimulation.

pMHC platform: The unique binding surface of DARPin molecules can be tailored to target pMHC immune complexes, which display the intracellular proteome on the surface of cells and thereby can show specific peptides intimately associated with disease, including with virus-infected cells or tumor cells. pMHCs have proved extremely challenging to target – with high affinity and specificity – for other modalities. The Company’s pMHC platform is now supported by technical proof-of-concept data demonstrating high potency and specificity – resolving several major challenges of classical pMHC-targeted discovery via non-DARPin approaches.

Board Updates
Gwen Fyfe has informed the Company that she will not stand for re-election at the upcoming Annual General Meeting on 21 April 2021. Gwen Fyfe has been a member of the Board of Directors since 2017. The Board of Directors would like to express their deep gratitude for her invaluable contributions and commitment to Molecular Partners during her years of service. Gwen Fyfe will be available to support the Company on a consultancy basis.

Financial Highlights: Net result and cash position on previous year’s level
In the financial year 2020, Molecular Partners recognized total revenues of CHF 9.3 million (2019: CHF 20.4 million) and incurred total expenses of CHF 67.7 million (2019: CHF 57.1 million). This led to an operating loss of CHF 58.3 million for 2020 (2019: Operating loss of CHF 36.7 million). The net financial loss of CHF 4.4 million recorded in 2020 compared to a net financial income of CHF 0.4 million in 2019. This resulted in a 2020 net loss of CHF 62.8 million (2019: Net loss of CHF 36.3 million).

The net cash used for operating activities in 2020 was CHF 29.0 million (2019: net cash used of CHF 1.2 million). Including time deposits, the cash and cash equivalents position increased by CHF 78.6 million vs. year-end 2019 to CHF 173.7 million as of December 31, 2020 (December 31, 2019: CHF 95.1 million). Total shareholders’ equity stood at CHF 107.2 million as of December 31, 2020, an increase of CHF 53.1 million (December 31, 2019: CHF 54.1 million).

As of December 31, 2020, the company employed 145 FTE, up 8% compared to year-end 2019. Approximately 85% of the employees are employed in R&D-related functions.

Business outlook and priorities
In 2021, Molecular Partners will focus on advancing its immuno-oncology and infectious disease programs. For the COVID-19 program, the Company anticipates final data from the ongoing phase 1 study of ensovibep will be available in the first quarter of 2021. The Company also anticipates the initiation of additional clinical studies of ensovibep throughout the first half of 2021, with the goal of achieving clinical proof of concept and potential emergency use authorization within 2021.

In immuno-oncology, the Company is planning to investigate an optimized dosing schedule for MP0310/AMG 506 via exploration of weekly administration ahead of potential combination studies with Amgen assets. The Company also expects initiation of a phase 1 study of MP0317, the second immuno-oncology local agonist, in H2 2021.

Additionally, Molecular Partners will continue to advance its immuno-oncology research pipeline, including the significantly advanced peptide MHC (pMHC) and CD3/T Cell targeting platforms, both of which have the potential to open up a range of new targets to DARPin therapeutics, and plans to publish or present multiple updates across its portfolio at select scientific venues.

Financial outlook 2021
For the FY 2021, at constant exchange rates, the company expects total P&L expenses of CHF 65-75 million, of which around CHF 7 million will be non-cash effective costs for share-based payments, IFRS pension accounting and depreciations. In terms of cash outflow the company expects a gross cash burn of CHF 85-95 million, which includes CHF 20 million payable to Novartis for the manufacturing of commercial supply. This cash flow guidance does not include any potential payments from R&D partnerships.

With CHF 173.7 million cash at hand and no debts as per the end of 2020 the company is funded into 2023, excluding any potential payments from R&D partners.

This guidance is subject to the progress of the pipeline, mainly driven by manufacturing costs, the speed of enrollment of patients in clinical trials and data from research and development projects.

Investor documentation of FY 2020 results
The results presentation as well as this press release will be made available at www.molecularpartners.com after 7:00am (CET) on February 05, 2021.

FY 2020 conference call
Molecular Partners will hold a conference call and video webcast on Friday, February 05, 2021, 2:00pm CET (1:00pm GMT, 8:00am EST).

In order to register for the FY 2020 conference call, please dial the following numbers approximately 10 minutes before the start of the presentation:

Participants will have the opportunity to ask questions after the presentation.

Video webcast
The FY 2020 results presentation will be webcast live and will be made available on the Company’s website under the investor section. The replay will be available for 90 days following the presentation.

On February 5, 2021 Vor Biopharma (Nasdaq: VOR), a cell therapy company pioneering engineered hematopoietic stem cell (eHSC) therapies combined with targeted therapies for the treatment of cancer, reported the pricing of its initial public offering of 9,828,017 shares of its common stock at a price to the public of $18.00 per share (Press release, Vor BioPharma, FEB 5, 2021, View Source [SID1234574708]). The gross proceeds to Vor from the offering, before deducting the underwriting discounts and commissions and other offering expenses payable by Vor, are expected to be approximately $176.9 million. In addition, Vor has granted the underwriters a 30-day option to purchase up to an additional 1,474,202 shares of its common stock at the initial public offering price, less the underwriting discounts and commissions. All of the shares of common stock are being offered by Vor.

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The shares are expected to begin trading on the Nasdaq Global Market on Friday, February 5, 2021, under the ticker symbol "VOR". The offering is expected to close on Tuesday, February 9, 2021, subject to customary closing conditions.

Goldman Sachs and Co. LLC, Evercore ISI, Barclays and Stifel are acting as joint book-running managers for the offering.

Registration statements relating to the securities being sold in this offering have been filed with the Securities and Exchange Commission (SEC) and have become effective. Copies of the registration statements can be accessed through the SEC’s website at www.sec.gov. This offering is being made only by means of a prospectus forming part of the effective registration statements relating to these shares. Copies of the final prospectus may be obtained, when available, from Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, via telephone at 1-866-471-2526, or via email at [email protected]; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, New York 10055, via telephone at 1-888-474-0200, or via email at [email protected]; Barclays Capital Inc., Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, via telephone at 1-888-603-5847, or via email at [email protected]; or Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, California 94104, via telephone at 1-415-364-2720, or via email at [email protected].

This press release shall not constitute an offer to sell, or a solicitation of an offer to buy these securities, nor shall there be any offer or sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.