Altimmune Announces Third Quarter 2021 Financial Results And Provides A Corporate Update

On November 9, 2021 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, reported financial results for the three- and nine-months ending September 30, 2021 and provided a corporate update (Press release, Altimmune, NOV 9, 2021, View Source [SID1234595124]).

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"The third quarter was a momentous time for our pemvidutide (ALT-801) program, as we delivered on positive topline data for the 12-week Phase 1 trial, cleared an IND in non-alcoholic steatohepatitis (NASH) with the FDA and initiated a 12-week Phase 1b study in non-alcoholic fatty liver disease (NAFLD)," remarked Vipin K. Garg, Ph.D., President and Chief Executive Officer at Altimmune. "In addition to the previously announced 12-week data showing double-digit weight loss in the 1.8 mg arm without the need for dose titration, we now have MRI-PDFF data in a subset of subjects with hepatic steatosis, or fatty liver, from that study demonstrating a remarkable reduction in liver fat to undetectable levels after only 6 weeks of pemvidutide treatment. These findings show the potential of pemvidutide in the treatment of both obesity and NASH, and we look forward to sharing the data from our ongoing Phase 1b trial in NAFLD and initiating Phase 2 trials for obesity and NASH in 2022."

Program Highlights:

Pemvidutide1 (ALT-801)

Announced weight loss data from 12-week Phase 1 clinical trial of pemvidutide in overweight and obese subjects

Subjects achieved mean weight losses of 4.9%, 10.3%, and 9.0% at 1.2 mg, 1.8 mg, and 2.4 mg doses, respectively
Once-weekly dosing regimen was well-tolerated without dose titration
Clinically meaningful reductions in serum lipids and blood pressure
No discontinuations due to adverse events
Obesity program advancing towards 48-week Phase 2 trial in the first half of 2022

Investigational New Drug application (IND) for obesity expected to be submitted by year end 2021
48-week Phase 2 obesity study expected to commence in the first half of 2022
1 proposed INN

Reduction in liver fat by MRI-PDFF exploratory analysis in recently completed Phase 1 study

MRI-PDFF data on liver fat content have now been analyzed through 6 weeks of treatment. While the trial inclusion criteria did not pre-specify a minimum liver fat content, the study did enroll a number of subjects with hepatic steatosis or fatty liver, defined as liver fat content greater than or equal to 5%. Five subjects had baseline hepatic steatosis (liver fat content ranging from 5.5 to 19.5%) and received pemvidutide at 1.8 mg or 2.4 mg dose levels. In each of these subjects, liver fat levels fell to undetectable levels within 6 weeks of treatment, representing a greater than 90% reduction in the liver fat content. These findings reinforce the results from preclinical studies of pemvidutide, which demonstrated statistically greater reductions in liver fat than an equivalent dose of semaglutide and confirm the combined beneficial effects of weight loss and glucagon on liver fat metabolism.

Pemvidutide IND application for NASH cleared and enrollment initiated in Phase 1b clinical trial in NAFLD, with topline data expected in the first half of 2022

The Phase 1b, 12-week NAFLD trial is being conducted in the US, with Dr. Stephen A. Harrison serving as Principal Investigator
The study will include diabetic and non-diabetic subjects, with a primary efficacy end point of the change in liver fat as measured by MRI-PDFF, and a key secondary endpoint of weight loss at Week 12
A 52-week biopsy driven Phase 2 NASH trial is expected to follow the conclusion of the NAFLD trial

Additional activities for continued development of pemvidutide

Drug-drug interaction trial of pemvidutide has been initiated in Australia, with results expected in the first half of 2022
A 12-week study to be initiated in Q1 2022 in the US to further characterize safety and pharmacokinetics of pemvidutide in diabetic subjects
HepTcell

Enrollment progressing in international Phase 2 clinical trial in chronic hepatitis B subjects, with topline data expected in the second half of 2022
Study readouts to include virological markers of hepatitis B infection
Financial Results for the Three and Nine Months Ended September 30, 2021

Altimmune had cash, cash equivalents, short-term investments and restricted cash totaling $199.9 million at September 30, 2021 compared to $216.0 million at December 31, 2020.
Revenue was $0.2 million for the three months ended September 30, 2021 compared to $2.9 million in the same period in 2020. The change in revenue quarter over quarter was primarily due to a decrease in MTEC/DoD revenue during the current period due to the timing of clinical trials and development activities for T-COVID.
Research and development expenses were $29.2 million for the three months ended September 30, 2021, compared to $17.0 million in the same period in 2020. The change was primarily the result of increased expenses related to development activities for the Company’s COVID-19 programs, offset by a decrease in the fair value of contingent consideration liability connected with the acquisition and development of pemvidutide.
General and administrative expenses were consistent period-over-period with $4.2 million recognized for the three months ended September 30, 2021 and $4.2 million in the same period in 2020.
Net loss for the three months ended September 30, 2021 was $33.5 million, or $0.81 net loss per share, compared to $17.8 million in the same period in 2020, or $0.54 net loss per share. Net loss for the nine months ended September 30, 2021 was $73.2 million, or $1.79 net loss per share, compared to $38.4 million in the same period in 2020, or $1.74 net loss per share.

Following the conclusion of the call, the webcast will be available for replay on the Investor Relations page of the Company’s website at www.altimmune.com. The Company has used, and intends to continue to use, the IR portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD.

About Pemvidutide
Pemvidutide (proposed INN, formerly known as ALT-801) is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist for obesity and non-alcoholic steatohepatitis (NASH). Altimmune believes the treatment of obesity is the cornerstone of treating NASH and its co-morbidities and views these conditions as significant unmet medical needs.

About HepTcell
HepTcell is a novel immunotherapeutic comprised of nine synthetic peptides representing conserved hepatitis B (HBV) sequences formulated with IC31, a TLR9-based adjuvant from Valneva SE. The HBV-directed peptides are designed to drive T cell responses against all HBV genotypes towards a functional cure for chronic HBV in patients of diverse genetic backgrounds.

FY2021 1H Results

On November 9, 2021 Kureha Corporation reported (Press release, Kureha Corporation, NOV 9, 2021, View Source [SID1234595210])

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FY2021 half-year operating profit at ¥11.4bn (up 84% YOY, up 52% from initial forecast); Full-year forecast revised upward to ¥19.5bn (up 13% YOY, up 30% from initial forecast)
◼ FY2021 year-end dividend forecast raised to ¥100 per share, up from ¥85 in prior year
◼ FY2021 business conditions characterized by:-Pandemic-impacted consumer behaviors (under stay-home restrictions) and robust outdoor leisure demand persisting during 1H, which is likely to diminish in 2H-Continued strong demand for automotive lithium-ion batteries as EV production and sales expand across the globe, driven by nations’ environment and economic initiatives-Surging fuel and raw materials prices due to tight oil supply, natural resources deficit and logistics/supply chain disruptions in post-pandemic recovery-Impact of reduced car production on Kureha Group businesses is limited and minimal
◼ Kureha Group has implemented strategic measures to:-Increase sales volumes of high-margin grades and items in PVDF, PPS, ‘NEW Krewrap’ and other product lines, while reducing cost via improved efficiency and expanded production output-Adjust sales prices to align with rising fuel and raw material costs Further risks:-Restriction of energy use in China may affect local manufacturing operations (Changshu PVDF facilities) and procurement of raw materials for PVDF manufacturing in Japan (Iwaki Factory)- Delays in reflecting a further and rapid rise in fuel/raw material prices

Factors attributing to changes in operating profit
AM: Increased sales volumes of PVDF, PPS and other advanced materials
SC: Industrial chemicals returned to generating profit
SP: Higher home products and packaging film volumes
CO: Profit maintained despite delays in civil engineering projects
OO: Absence of prior year’s post-typhoon waste treatment projects

Factors attributing to changes in operating profit
AM: Better-than-expected volume growth for PVDF and carbon products, an increase in equity in PPSrelated affiliate’s earnings
SC: Front-loaded deliveries of agrochemicals (2H→1H) SP: Continued pandemic-impacted demand for home products, fewer expenses
CO: Improved sales cost due to mix changes and cost reduction
OO: Higher sales volumes in the low-PCB waste treatment business

CStone Pharmaceuticals and DotBio sign a global discovery collaboration and option agreement to expand emerging portfolio of next-generation innovative therapeutics

On November 9, 2021 CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on the research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, and DotBio Pte. Ltd ("DotBio"), a biotech company specialized in next generation antibody therapies, reported that they have entered into a collaboration agreement (Press release, DotBio, NOV 9, 2021, View Source [SID1234646737]). This collaboration represents the first project to be settled at CStone Global R&D Headquarters and Industrialization Base in Suzhou. CStone will lead the design of target combination based on the intended mechanism of action and DotBio will lead the molecular design and engineering. It will become a source of innovative preclinical candidates to support CStone’s Pipeline 2.0 strategy, further accelerating drug discovery with denovo design.

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Under the partnership, the two sides will jointly develop up to three first-in-class or best-inclass next-generation antibody therapies, including multi-functional antibodies and antibodydrug conjugates (ADCs). CStone will take an equity position in DotBio and has the option to acquire global rights to the molecules at predefined terms.

DotBio’s proprietary DotBody technology platform is based on the concept of modular design. By prefabricating antibody modules with specific functions, DotBio is able to combine them on demand to build multi-functional antibodies quickly and efficiently, improving antibody quality, development success rate and efficiency. This high throughput process allows DotBio to generate multi-specific antibodies, ADCs and intracellular antibodies in a matter of months as opposed to over a year. The DotBody platform has been optimized for autonomous folding, better stability, high expression levels, high concentration, and low aggregation.

Dr. Archie Tse, Chief Scientific Officer of CStone, said: "In our organic research model, we utilize the scientific expertise and clinical insights of our experienced R&D team to select targets and design projects, while leveraging external synergies, particularly by working with platform companies with unique technological advantages, to develop high-quality innovative drugs. Technology platform collaborations of this nature, among other sources of innovation, will become an integral part of CStone’s discovery research engine. We are very excited about the potential of DotBio’s domain therapeutic antibody platform which is a perfect strategic fit to the modular, multi-specific, and multi-functional nature of the biologic products in our Pipeline 2.0. We believe that the collaboration between us will help advance the development of next-generation antibody therapies and bring the most effective medicines to cancer patients as early as possible."

Dr. Ignacio Asial, CEO and founder of DotBio, said, "DotBio aims to accelerate the development of next-generation cancer therapies through our modular design, multi-functional antibody discovery platform. This collaboration with CStone, a company with a wealth of expertise in cancer biology and clinical development, is an important step towards achieving this goal. The incubation of DotBio at CStone’s Global R&D Headquarters and Industrialization Base will offer both our teams a unique opportunity to work closely together. At the same time, this will provide DotBio with a strong foundation to expand into the China market. We are very excited about this collaboration and look forward to working with CStone to deliver more effective, DotBody-based treatments to patients."

Under the agreement, CStone will provide DotBio with a fully functional lab space and in-kind
resource sharing at CStone Global R&D Headquarters and Industrialization Base during the
collaboration period. DotBio will be eligible to earn milestone payments as the drug candidates
advance through development. If approved, DotBio is eligible for royalty payments.

Istari Oncology Presents Data on Its PVSRIPO Immunotherapy at the Annual November Meetings for the Society for Immunology of Cancer (SITC) and the Society for Neuro-Oncology (SNO)

On November 9, 2021 Istari Oncology, Inc., a clinical-stage biotechnology company developing novel immunotherapies for the treatment of solid tumors, reported it will be presenting data on its investigative immunotherapy PVSRIPO for the potential treatment of solid tumors at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC; Washington D.C.; November 10-14) and the 26th Annual Meeting of the Society for Neuro-Oncology (SNO; Boston; November 18 – 21) (Press release, Istari Oncology, NOV 9, 2021, View Source [SID1234594830]).

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PVSRIPO is an investigational immunotherapy based on the live–attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO has been shown to activate a patient’s innate and adaptive immune system to facilitate a systemic anti-tumor immune response. Because PVSRIPO utilizes CD155 (the poliovirus receptor) to enter both solid tumor cells and antigen–presenting cells (APCs) in the tumor microenvironment, PVSRIPO has the potential to treat a variety of cancers.

Details of Istari Oncology’s SITC (Free SITC Whitepaper) Presentations – Focusing on PVSRIPO’s recall MOA and recent expansion into head and neck cancer
Title: Poster Presentation: (517) LUMINOS-103: A basket trial evaluating the safety and efficacy of PVSRIPO and PVSRIPO in combination with anti-PD-1/L1 checkpoint inhibitors in patients with advanced solid tumors
Presenter: Brant A. Inman MD, MS
Presentation time: 11/12/2021 from 7:00 – 8:30 p.m. EST
Location: Poster Hall, Walter E. Washington Convention Center, Washington D.C.

Title: Poster Presentation: (739) Intratumor childhood vaccine-specific CD4+ T cell recall helps antitumor CD8 T cells
Presenter: Michael Brown, PhD
Presentation time: 11/12/2021 from 7:00 a.m. – 8:30 p.m. EST
Location: Poster Hall, Walter E. Washington Convention Center, Washington D.C.

Details of Istari Oncology’s SNO Presentations – Focusing on preclinical and clinical safety data supporting the company’s work in glioblastoma
Title: Poster Presentation: (CTIM-18) LUMINOS-101: Initial safety and tolerability of PVSRIPO and pembrolizumab combination therapy in recurrent glioblastoma
Presenter: Andrew Sloan, MD
Presentation time: 11/18 – 11/21 from 7:30 – 9:30 p.m. EST
Location: Exhibit Hall D, Hynes Convention Center, Boston, MA

Title: Poster Presentation: (BIOM-20) Tumor-intrinsic and peripheral features associate with survival after polio virotherapy in recurrent GBM
Presenter: Michael Brown, PhD
Presentation time: 11/18 – 11/21 from 7:30 – 9:30 p.m. EST
Location: Exhibit Hall D, Hynes Convention Center, Boston, MA

Title: Abstract Presentation: (IMMU-26) Safety and efficacy of PVSRIPO in recurrent glioblastoma: long-term follow-up and initial multicenter results
Presenter: Annick Desjardins, MD, FRCPC
Presentation time: 11/19 from 4:50 – 4:55 p.m. EST
Location: Room 207, Hynes Convention Center, Boston, MA

Title: Abstract Presentation: (EXTH-77) Polio virotherapy of murine brain tumors includes microglia proliferation and inflammation that is potentiated by immune checkpoint blockade
Presenter: Yuanfan Yang, MD
Presentation time: 11/21 from 11:50 – 11:55 a.m. EST
Location: Room 208, Hynes Convention Center, Boston, MA

For more information about Istari Oncology and its ongoing clinical trials, visit www.istarioncology.com.

About PVSRIPO
PVSRIPO is an investigational immunotherapy based on the live-attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO targets cells using the poliovirus receptor CD155, which is widely expressed on both the malignant cells of most solid tumors and key antigen-presenting cells (APCs) within the tumor microenvironment. PVSRIPO targets tumors using three key mechanisms: 1) engagement and activation of APCs, leading to T cell priming and sustained, systemic anticancer immunity; 2) direct tumor cell killing and antigen release; and 3) amplification of the immune response via recall of poliovirus vaccine-specific T cells. PVSRIPO has been granted Breakthrough Therapy and Orphan Drug Designation status by the U.S. Food and Drug Administration in recurrent glioblastoma, and Fast Track and Orphan Drug Designation status in refractory melanoma.

BioNTech Announces Third Quarter 2021 Financial Results and Corporate Update

On November 9, 2021 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company"), a next-generation immunotherapy company pioneering novel therapies for cancer and infectious diseases, reported financial results for the third quarter and first nine months of 2021 ended September 30, 2021 (Press release, BioNTech, NOV 9, 2021, View Source [SID1234594846]).

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"We continue to work diligently to respond to global vaccine needs with a commitment to ensure equitable vaccine access. Our robust clinical and regulatory strategy has led to recent approvals that expand access to additional age groups, highlighted by the first EUA for a COVID-19 vaccine in children 5 to under 12 years of age in the United States, and authorizations for booster doses for multiple populations," said Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. "We also had a strong quarter with regard to our oncology pipeline. Our approach to oncology addresses each patient’s unique needs by leveraging multiple therapeutic platforms with combination potential. With the recent dosing of the first patient with autogene cevumeran in high-risk colorectal cancer patients after adjuvant treatment, we now have four programs in Phase 2 development, as our pipeline advances into later-stage trials. We are reporting positive clinical data across 6 of our oncology programs at the upcoming SITC (Free SITC Whitepaper) conference, including favorable safety profiles and robust immune responses."

Third Quarter 2021 and Subsequent Updates

Infectious disease

Infectious disease is a growth pillar for BioNTech, and the company is developing vaccine candidates to address multiple pathogens that pose significant global public health challenges.

COVID-19 Vaccine Program – BNT162b2
BNT162b2 clinical development updates

Multiple clinical trials are ongoing to expand COVID-19 vaccine reach and explore booster doses to address waning immunity. Clinical data to date support a third dose booster of the vaccine in adults to augment vaccine protection over time. A third booster dose of BNT162b2 confers high neutralizing antibody titers against SARS-CoV-2 ancestral virus and the Beta and Delta variants. The titers following a booster dose are higher than the levels observed after the two-dose primary series.
Additionally, studies are underway evaluating variant-specific versions of the vaccine to generate data to inform BioNTech and Pfizer’s strategy to address emerging SARS-CoV-2 variants. While to date, there is no clinical data suggesting the need for a variant-specific version of the vaccine, the companies are establishing a preemptive prototype approach to evaluate the development, manufacturing and regulatory processes for variant specific vaccines. This prototype approach is aimed to be substantiated by broad clinical data that are being prepared for submission to regulatory authorities.

In August 2021, BioNTech and Pfizer started a clinical trial to evaluate the safety and immunogenicity of variant-encoding vaccine candidates, including a multivalent vaccine against two variants of concern. The study will enroll approximately 1,200 adults 18 to 85 years of age. Participants will receive a third 30 µg dose of a multivalent Delta and Alpha version of the vaccine, or monovalent Delta or Alpha versions administered six months after the second dose of the two-dose primary series of BNT162b2. Vaccine- and SARS-CoV-2-naïve participants in the study will receive two doses of the multivalent Delta and Alpha vaccine administered 21 days apart. First data from this study are anticipated in the fourth quarter of 2021.
On September 6, 2021, BioNTech and Pfizer announced data from a Phase 3 safety and immunogenicity clinical trial of 306 participants 18 to 55 years of age who received a booster dose approximately six months after completing the two-dose primary regimen, with a median follow-up time of 2.6 months post-third dose. The booster dose elicited significantly higher SARS-CoV-2 neutralizing antibody titers against the ancestral strain compared to the levels observed after the two-dose primary series with titers against ancestral virus more than 5 times as high at 1 month after the third dose compared to 1 month after the two-dose primary series. The safety profile was favorable and similar to the safety profile after dose two of the primary series and generally consistent with other clinical data for BNT162b2. Previously reported Phase 1 data showed a similar pattern of third dose responses against the ancestral strain, Beta and Delta variants. Based on these data a third dose booster of BNT162b2 for emergency use in certain population groups was authorized by the U.S. Food and Drug Administration (FDA) and the Conditional Marketing Authorization (CMA) in the European Union was updated upon approval from the European Commission (EC) following a positive opinion from the European Medicines Agency (EMA) for a booster dose of the COVID-19 vaccine from BioNTech and Pfizer. The data are also being submitted to other regulatory authorities worldwide.
On September 20, 2021, BioNTech and Pfizer announced positive topline results from a Phase 2/3 trial in children demonstrating strong immune response one month after the second dose in 2,268 children aged 5 to under 12 years. The vaccine showed a favorable safety profile and robust neutralizing antibody responses in this cohort using a two-dose regimen of 10 µg administered 21 days apart. Antibody responses were comparable to those in a previous study in people 16 to 25 years of age immunized with 30 µg doses. One month after the second dose, the geometric mean ratio of SARS-CoV-2 neutralizing titers in the children aged 5 to under 12 years to those in people 16 to 25 years of age was 1.04, meeting the predefined immunobridging success criteria. These data compare immune responses between a vaccine candidate and an approved vaccine. These data were recently submitted for publication in a peer-reviewed journal.
Subsequently, on October 26, 2021, the companies reported further results from the Phase 2/3 trial in children that included an additional 2,379 children, from the supplemental safety group, bringing the total to approximately 4,500. In this analysis, BNT162b2 showed a favorable safety profile, robust immune responses as well as a vaccine efficacy rate of 90.7% in participants without prior SARS-CoV-2 infection, measured 7 days after the second dose, during a period when Delta was the prevalent strain. Topline readouts for the other two age cohorts from the trial – children 2 to <5 years of age and children 6 months to <2 years of age – are expected as soon as the fourth quarter of 2021 or early first quarter 2022.
On October 21, 2021, BioNTech and Pfizer announced topline results from a Phase 3 clinical trial to evaluate the safety, tolerability and efficacy of a 30 µg booster dose versus placebo in more than 10,000 participants aged 16 years and older who previously received two doses of BNT162b2 at least six months prior to randomization. These first results from a randomized, controlled COVID-19 vaccine booster dose trial demonstrated that a booster dose restored vaccine protection to the high levels achieved after the second dose, showing a relative vaccine efficacy of 95.6% compared to those who did not receive a booster dose. Multiple subgroup analyses showed efficacy was consistent irrespective of age, sex, race, ethnicity and co-morbidities. The adverse event profile was consistent with previous clinical safety data. The companies plan to share these data with the FDA, EMA, and other regulatory agencies and submit detailed results for publication in a peer-reviewed journal.
A global Phase 2/3 trial to evaluate the safety, tolerability and immunogenicity of BNT162b2 in preventing COVID-19 in healthy pregnant women 18 years of age and older is ongoing. The study will also assess safety in infants of vaccinated pregnant women and the transfer of potentially protective antibodies to their infants.
Regulatory updates

BioNTech and Pfizer have made progress on the regulatory front, including Biologics License Application (BLA) approval in the United States, as well as U.S. Emergency Use Authorization (EUA) for booster doses for many populations at high risk of severe COVID-19-disease. The EMA issued a positive opinion on the administration of BNT162b2 as a booster dose in adults and as a third dose in immunocompromised people.

In August 2021, the U.S. FDA and the EMA authorized the extension of the shelf-life of the COVID-19 vaccine from six to nine months when stored at -90 to -60 degrees C.
On August 23, 2021, the U.S. FDA approved the BLA for BNT162b2 to prevent COVID-19 in individuals 16 years of age and older based on a comprehensive data package that included longer-term follow-up data from the Phase 3 trial. BNT162b2 is the first COVID-19 vaccine to be granted full approval by the FDA.
On September 22, 2021, the U.S. FDA authorized a third dose booster for emergency use in individuals 65 years of age and older, individuals 18 through 64 years of age at high risk of severe COVID-19, and individuals 18 through 64 years of age whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications from COVID-19 including severe COVID-19. The booster dose, which is the same formulation and dosage as used in the primary series, is to be administered at least six months after completion of the primary series. A third dose was authorized on August 12, 2021, under the EUA for administration to individuals at least 12 years of age who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.
On October 5, 2021, the EC granted a variation to the CMA for the administration of a third dose booster of BNT162b2 at least six months after the second dose in individuals 18 years of age and older. This followed a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the EMA. The positive opinion follows the companies’ submission of a variation to the EMA requesting to update the CMA with data supporting a booster dose to prevent COVID-19 in individuals 16 years of age and older. The CHMP also recommended that people with severely weakened immune systems should be given a third dose of the vaccine at least 28 days after their second dose.
In October 2021, BioNTech and Pfizer announced the submission of data supporting the vaccination of children 5 to under 12 years of age to the EMA for a variation of the CMA in the European Union. The variation request includes data from the Phase 2/3 study, which is enrolling children 6 months to under 12 years of age. The data will also be filed with other regulatory authorities in the coming weeks.
On October 29, 2021, BioNTech and Pfizer received the first U.S. FDA EUA of a COVID-19 vaccine in children ages 5 through 11 years of age based on data from a Phase 2/3 randomized, controlled trial. This EUA follows the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) vote on October 26, 2021, recommending that the FDA grant EUA in this population.
In November 2021, the EC authorized a new formulation of BNT162b2, that further simplifies vaccine handling. This decision followed a positive opinion from the EMA CHMP. The new formulation also allows for longer storage, as vials can be stored for 10 weeks at refrigerator temperatures from 2°C to 8°C, and after first puncture, can be stored and transported at 2°C to 30°C and used within 12 hours.
Commercial updates

BioNTech and Pfizer have delivered an aggregate of over 2 billion doses of BNT162b2 vaccine to more than 152 countries and territories around the world as of November 2, 2021.
Further discussions for additional dose commitments are ongoing for 2022 and beyond.

On September 22, 2021, BioNTech and Pfizer announced plans to expand the existing agreement with the U.S. government by providing an additional 500 million doses at a not-for-profit price for donation to low- and lower-middle-income countries and the organizations that support them. This expanded agreement brings the total number of doses to be supplied to the U.S. government for donation to one billion. The companies are committed to working toward equitable and affordable access to COVID-19 vaccines for all people around the world, actively working with governments and health partners worldwide, and have pledged to provide two billion doses to low- and middle-income countries in 2021 and 2022.
In October 2021, the Japanese government agreed to purchase another 120 million doses starting in January 2022, bringing the total number of doses purchased to 314 million.
On October 28, 2021, BioNTech and Pfizer announced that the U.S. government purchased an additional 50 million doses to continue to support preparedness for pediatric vaccinations, including securing vaccines for children under 5 years of age. With this purchase, the U.S. government has exercised its final purchase option under the existing supply agreement, bringing the total number of doses secured under the agreement to 600 million, excluding the one billion doses to be supplied at a not-for-profit price for donation.
Manufacturing Updates

BioNTech and Pfizer expect to manufacture 2.7 billion to 3 billion doses by the end of 2021 and anticipate capacity to manufacture up to four billion doses in 2022. The companies have developed a global COVID-19 vaccine supply chain and manufacturing network, which now spans four continents and includes more than 20 manufacturing facilities.

On August 26, 2021, BioNTech and Pfizer announced the signing of a letter of intent with Eurofarma Laboratórios SA, a Brazilian biopharmaceutical company, to manufacture vaccine for distribution within Latin America. Eurofarma will obtain drug product from facilities in the United States, and manufacturing of finished doses is expected to commence in 2022. At full operational capacity, annual production is expected to exceed 100 million finished COVID-19 doses.
Influenza Vaccine Program

BNT161 – On September 27, 2021, the first participants were dosed in a Phase 1 clinical trial to evaluate the safety, tolerability and immunogenicity of a single dose quadrivalent mRNA vaccine (BNT161) against influenza in healthy adults 65 to 85 years of age, with an FDA-approved standard quadrivalent influenza vaccine as a control. BNT161 encodes World Health Organization recommended strains. Data from the trial is expected in the first half of 2022. BNT161 is partnered with Pfizer.
Other Infectious Disease

BioNTech is committed to developing vaccines and sustainable end-to-end vaccine production on the African continent and to provide affordable access to low- and lower-middle-income countries. The company has continued its efforts to establish the necessary infrastructure and to grow its infectious disease pipeline.

On July 26, 2021, BioNTech announced plans to develop sustainable solutions to address infectious diseases on the African continent. BioNTech aims to develop an mRNA-based malaria vaccine and the initiation of a clinical trial is expected by end of 2022.
On October 26, 2021, BioNTech announced that construction of the first mRNA manufacturing facility in Africa is expected to begin in mid-2022, following the signing of a Memorandum of Understanding with the Rwandan government and the Institut Pasteur de Dakar (Senegal). BioNTech believes this facility could become the first node in a decentralized and robust African end-to-end manufacturing network with an expected annual manufacturing capacity of several hundreds of million mRNA vaccine doses to provide sustainable vaccine supply on the African continent.
The company also announced that clinical trials for its first tuberculosis vaccine candidate are planned to begin by end of 2022, just two years after the program was initiated. BioNTech has collaborated with the Bill and Melinda Gates Foundation since 2019 to develop preclinical vaccine and immunotherapy candidates to prevent HIV and tuberculosis infection.
Oncology

BioNTech is advancing the development of a broad oncology pipeline, which spans multiple anti-tumor and immune-modulating approaches. BioNTech’s clinical pipeline now includes randomized Phase 2 clinical trials for FixVac programs, BNT111 and BNT113, and for iNeST product candidate autogene cevumeran (BNT122, RO7198457), bringing the company’s clinical programs to a total of 15 product candidates in 19 ongoing clinical trials including four phase 2 randomized clinical trials.
BioNTech expects to further advance its oncology pipeline in the fourth quarter of 2021 with one preclinical program expected to move into a first-in-human Phase 1 trial.
Seven updates (from 6 oncology programs) with positive clinical and preclinical data supporting BioNTech’s oncology pipeline will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting which takes place on November 10–14, 2021. The information below regarding the SITC (Free SITC Whitepaper) presentations reflects data in submitted abstracts and supplemental data may be presented at the conference.

mRNA programs
FixVac

These product candidates leverage the company’s proprietary pharmacologically optimized uridine mRNA and its proprietary intravenous lipoplex formulation.

BNT111 – A global, three-arm Phase 2 trial evaluating BNT111 in combination with cemiplimab (Regeneron and Sanofi’s Libtayo), versus both agents as monotherapy, in patients with anti-PD1-refractory/relapsed unresectable Stage III or IV melanoma is ongoing. The trial is being conducted in collaboration with Regeneron.
On September 15, 2021, the U.S. FDA granted Orphan Drug Designation to BNT111 for the treatment of Stage IIB through IV melanoma.
At SITC (Free SITC Whitepaper), BioNTech intends to present additional data from the ongoing Phase 1 trial evaluating the safety and tolerability of BNT111 in patients with advanced melanoma. Data demonstrated that the immunogenicity and safety profile of BNT111 as a monotherapy were comparable in patients grouped as having evidence of disease (ED) and in patients with no evidence of disease (NED). As of May 24, 2021, 14 of 22 (64%) patients with ED and 19 of 28 (68%) patients with NED demonstrated BNT111-induced T-cell responses against at least one tumor-associated antigen (TAA). In NED patients, clinical efficacy was promising with median disease-free survival of 34.8 months.

BNT112 – At SITC (Free SITC Whitepaper), BioNTech intends to present data from the ongoing Phase 1/2 trial of BNT112 as a monotherapy and in combination with cemiplimab in patients with metastatic castration-resistant prostate cancer (mCRPC) and newly diagnosed high-risk localized prostate cancer (LPC). Overall, as of June 22, 2021, the data suggest that BNT112 as monotherapy and in combination with a PD-1 inhibitor (cemiplimab) is well-tolerated in mCRPC. Additionally, data suggest that BNT112 induces robust immune responses, as de novo induction and expansion of pre-existing antigen-specific T-cell responses was observed in all patients with available Post-IVS-ELISpot.
BNT113 – A randomized Phase 2 trial evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ head and neck squamous cell carcinoma (HNSCC) expressing PD-L1 is ongoing.
Individualized neoantigen specific immunotherapy (iNeST)

Autogene Cevumeran (BNT122) – BioNTech’s iNeST product candidate autogene cevumeran is also based on the company’s proprietary pharmacologically optimized uridine mRNA and its proprietary intravenous lipoplex formulation, and is partnered with Genentech. In October 2021, BioNTech announced that the first patient was dosed in a randomized Phase 2 trial in the adjuvant treatment of circulating tumor DNA (ctDNA) positive, surgically resected Stage II (high-risk)/Stage III colorectal cancer. The trial plans to enroll about 200 patients to evaluate the efficacy of autogene cevumeran compared to watchful waiting after surgery and chemotherapy, the current standard of care for these high-risk patients. The primary endpoint for the study is disease-free survival. Secondary objectives include overall survival and safety. The trial has been initiated in the United States, Germany, Spain and Belgium.
The medical need for novel therapies to treat colorectal cancer, the second deadliest cancer worldwide, remains high. The current standard of care in this indication is watchful waiting to see if tumors recur after removal of the primary tumor and adjuvant chemotherapy. A proportion of these patients are expected to have a recurrence of their tumor within 2 to 3 years after their surgery. For this clinical trial, patients at high risk for recurrence will be selected by means of a highly sensitive blood test detecting ctDNA.

RiboMabs

BioNTech’s RiboMab product candidates, BNT141 and BNT142, are designed to encode secreted antibodies. These product candidates leverage the company’s proprietary nucleoside-modified mRNA which is designed to minimize the immunomodulatory activity of the mRNA.

BNT141 – BioNTech plans to start a Phase 1 clinical trial for BNT141 in the fourth quarter of 2021.
BNT142 – BioNTech now plans to start a Phase 1 clinical trial for BNT142 in the first half of 2022.
Antibodies
Next-generation checkpoint immunomodulators

BNT311 and BNT312 are partnered with Genmab as part of a 50/50 collaboration in which development costs and future profit are shared.

BNT311/GEN1046 – A Phase 1/2 trial with multiple expansion cohorts in patients with solid tumors is ongoing.
At SITC (Free SITC Whitepaper), BioNTech intends to present exploratory pharmacodynamic analyses and potential biomarkers of response in an expansion cohort of patients with metastatic or unresectable NSCLC who had multiple lines of prior systemic therapy, including a checkpoint inhibitor. As of May 2021, 40 patients were enrolled and BNT311 elicited pharmacodynamic effects consistent with its proposed mechanism of action. In addition, relationships between disease control and PD-L1 tumoral expression, as well as time from last prior anti-PD-1 therapy were observed.
A Phase 2 trial of BNT311 as monotherapy and in combination with pembrolizumab in patients with recurrent/refractory metastatic non-small cell lung cancer is planned to start in the fourth quarter of 2022.

BNT312/GEN1042 – A Phase 1/2 trial with multiple expansion cohorts in patients with solid tumors is ongoing.
At SITC (Free SITC Whitepaper), BioNTech intends to report, in a mini-oral presentation, clinical data from the dose escalation part of the ongoing Phase 1/2 trial. Overall the data demonstrated a favorable safety profile in patients with advanced solid tumors, as well as biologic and early antitumor activity. As of June 11, 2021, disease control was achieved in 25 of 49 (51%) patients, including two confirmed partial responses per RECIST1.1 in melanoma and neuroendocrine lung cancer.

Cell therapies
CAR-T cell immunotherapy

BNT211 – A first-in-human Phase 1/2 open-label dose escalation and dose expansion trial evaluating BNT211 in patients with Claudin-6-positive solid tumors is ongoing.
At SITC (Free SITC Whitepaper), BioNTech intends to present data from this trial. Overall, as of July 23, 2021, Claudin-6 CAR-T cells dosed as monotherapy and in combination with Claudin-6 CARVac showed a favorable safety profile at doses tested with encouraging signs of efficacy. At the first tumor assessment six weeks after adoptive T-cell transfer for the five evaluable patients, four patients showed stable disease (SD) and one patient showed progressive disease (PD). Three patients showed initial tumor shrinkage per RECIST1.1.

Neoantigen-targeting T-cell therapy

BNT221 – A first-in-human Phase 1 dose escalation trial evaluating BNT221 in patients with checkpoint inhibitor unresponsive or refractory metastatic melanoma is ongoing. At SITC (Free SITC Whitepaper), preclinical data demonstrating NEOSTIM’s ability to induce CD8+ and CD4+ T-cell responses using peripheral blood mononuclear cells from patients with ovarian cancer will be presented. These responses were polyfunctional, specific and have the capacity to degranulate.
Small molecule immunomodulators
Toll-like receptor binding agonist

BNT411 – A Phase 1/2 dose-escalation trial of BNT411 as a monotherapy in patients with solid tumors and in combination with atezolizumab, carboplatin and etoposide in patients with chemotherapy-naïve extensive-stage small cell lung cancer (ES-SCLC) is ongoing.
At SITC (Free SITC Whitepaper), BioNTech intends to present preliminary clinical data from the Phase 1/2 trial. Overall, as of July 1, 2021, BNT411 demonstrated an acceptable safety profile at all doses tested as a monotherapy and in combination with atezolizumab, carboplatin and etoposide. Pharmacodynamic signals were encouraging and showed a strong induction of type 1 interferon-dominated cytokines in line with the proposed mechanism of action. BNT411 has shown early signal of prolonging stable disease even in heavily pre-treated patients including post-anti-PD-1. Both pharmacodynamics and anti-tumor responses warrant further expansion in various indications either as a monotherapy or in combination with other standard-of-care treatments.

Corporate Updates

In October 2021, BioNTech expanded its infectious disease portfolio capabilities by acquiring PhagoMed Biopharma GmbH, an Austrian biotechnology company, specialized in the development of a new class of antibacterials.
Third Quarter 2021 Financial Results

Revenues: Total revenues were estimated to be €6,087.3 million1 for the three months ended September 30, 2021, compared to €67.5 million for the three months ended September 30, 2020. For the nine months ended September 30, 2021, total revenues were estimated to be €13,444.2 million1 compared to €136.9 million for the comparative prior year period. The increase was mainly due to rapid increases in the supply and sales of the COVID-19 vaccine worldwide. Under the collaboration agreements, territories have been allocated between BioNTech, Pfizer and Fosun Pharma based on marketing and distribution rights. During the three months ended September 30, 2021, BioNTech’s commercial revenues included an estimated amount of €4,341.5 million1 gross profit share and €17.0 million of sales milestones. During the nine months ended September 30, 2021, BioNTech’s commercial revenues included an estimated amount of €9,769.9 million1 gross profit share and €432.8 million of sales milestones. BioNTech’s share of the collaboration partners’ gross profit is based on COVID-19 vaccine sales in Pfizer’s and Fosun Pharma’s territories and represents a net figure. In addition, during the three and nine months ended September 30, 2021, respectively, €312.3 million and €514.3 million sales to BioNTech’s collaboration partners of products manufactured by BioNTech as well as €1,350.8 million and €2,586.2 million direct COVID-19 vaccine sales to customers in BioNTech’s territory, Germany and Turkey, have been recognized.

Cost of Sales: Cost of sales were estimated to be €1,211.4 million1 for the three months ended September 30, 2021, compared to €6.8 million for the three months ended September 30, 2020. For the nine months ended September 30, 2021, cost of sales were estimated to be €2,328.3 million1, compared to €18.3 million for the comparative prior year period. During the three and nine months ended September 30, 2021, estimated cost of sales of €1,194.8 million1 and €2,290.1 million1, respectively, were recognized with respect to BioNTech’s COVID-19 vaccine sales and include the share of gross profit that BioNTech owes its collaboration partner Pfizer based on its sales.

Research and Development Expenses: Research and development expenses were €260.4 million for the three months ended September 30, 2021, compared to €227.7 million for the three months ended September 30, 2020. For the nine months ended September 30, 2021, research and development expenses were €677.7 million, compared to €388.0 million for the comparative prior year period. The increase was mainly due to an increase in research and development expenses from the BNT162 program. The increase was further driven by an increase in wages, benefits and social security expenses following an increase in headcount, the recognition of inventor compensation expenses as well as expenses incurred under share-based-payment arrangements.

General and Administrative Expenses: General and administrative expenses were €68.2 million for the three months ended September 30, 2021, compared to €23.5 million for the three months ended September 30, 2020. For the nine months ended September 30, 2021, general and administrative expenses were €154.9 million, compared to €58.1 million for the comparative prior year period. The increase was mainly due to an increase in wages, benefits and social security expenses following an increase in headcount and expenses incurred under the share-based-payment arrangements, increased expenses for purchased management consulting and legal services as well as higher insurance premiums caused by the increased business volume.

Income Taxes: Interim income taxes were accrued in an amount of €1,456.4 million and €3,206.2 million for the three and nine months ended September 30, 2021, respectively, and were recognized using the estimated annual effective income tax rate of approximately 31%.
Net Profit/(Loss): Net profit was €3,211.0 million for the three months ended September 30, 2021, compared to €210.0 million net loss for the three months ended September 30, 2020. For the nine months ended September 30, 2021, net profit was €7,126.3 million, compared to €351.7 million net loss for the comparative prior year period.

Cash Position: Cash and cash equivalents as of September 30, 2021 were €2,392.7 million. In addition, trade receivables remained outstanding which is mainly due to the contractual settlement of the gross profit share under the COVID-19 collaboration with Pfizer, which has a temporal offset of more than one calendar quarter. As Pfizer’s fiscal quarter for subsidiaries outside the United States differs from BioNTech’s financial reporting cycle, it creates an additional time lag between the recognition of revenues and the payment receipt. Consequently, these trade receivables which are subject to this temporal offset and were outstanding as of September 30, 2021 were received as payments in October 2021, improving BioNTech’s cash position.

Shares Outstanding: Shares outstanding as of September 30, 2021 were 242,516,955.

Updated Outlook for the 2021 Financial Year

The full interim unaudited condensed consolidated financial statements can be found in BioNTech’s Report on Form 6-K, filed today with the SEC and available at View Source

1Estimated figures based on preliminary data shared between the collaboration partner and BioNTech as fully described in the Annual Report on Form 20-F as well as the Quarterly Report as of and for the Three and Nine Months Ended September 30, 2021, filed as an exhibit to BioNTech’s Current Report on Form 6-K. Changes in the share of the collaboration partners’ gross profit will be recognized prospectively.
2Figures have been estimated at constant foreign exchange rates.