On August 9, 2021 bluebird bio, Inc. (NASDAQ: BLUE) reported financial results and business highlights for the second quarter ended June 30, 2021 and provided operational updates, including the announcement that the U.S. Food and Drug Administration (FDA) placed a clinical hold on clinical studies of elivaldogene autotemcel (eli-cel, Lenti-D) gene therapy (licensed as SKYSONA in Europe) for cerebral adrenoleukodystrophy (CALD) (Press release, bluebird bio, AUG 9, 2021, View Source [SID1234586078]).

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"I’m tremendously proud of what bluebird has accomplished this quarter both operationally and strategically to ready ourselves to launch both bluebird bio and 2seventy bio," said Nick Leschly, chief bluebird. "Seven months after announcing our intent to split, and thanks to the incredibly hard work by our teams, we have created a solid foundation for both organizations. The ABECMA launch is exceeding expectations, the oncology INDs and severe genetic disease (SGD) biologics license application (BLA) filings are tracking for later this year, and we have established clear visions and leadership teams for each business. Importantly, we have made tough strategic decisions to reshape the overall cost structure to allow both companies to launch in a strong position to execute through important value-creating milestones."

BUSINESS SEPARATION

In January 2021, bluebird announced its intent to separate into two independent, publicly traded companies (bluebird bio and 2seventy bio). The company expects the separation to be completed by the end of 2021 and to be tax-free to bluebird shareholders.

Key members of the executive teams of both companies have been announced, effective upon completion of the planned separation. This includes Andrew Obenshain as CEO of bluebird and Nick Leschly as CEO of 2seventy.
The full board of directors for both companies will be announced closer to the separation date.
2seventy has confidentially filed its Form 10 Registration Statement with the U.S. Securities and Exchange Commission (SEC), in which it describes the planned tax-free spin-off of 2seventy as a publicly traded company.
bluebird plans to distribute 100% of the outstanding shares of 2seventy common stock to bluebird’s stockholders on a pro-rata basis.
Based on current cash position and the expected $110M upfront payment upon closing of the National Resilience, Inc. strategic collaboration, the Company anticipates having a cash balance of approximately $900M at the time of separation. Together with existing and emerging sources of revenue, we expect our cash balance will be sufficient to fund approximately 24 months of operations for bluebird and 2seventy under current business plans.
ELI-CEL SAFETY UPDATE

The company received a reported Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS), that is likely mediated by Lenti-D lentiviral vector (LVV) insertion, in a patient who was treated with eli-cel, or Lenti-D drug product for CALD over one year ago in the Phase 3 ALD-104 study. Evidence currently available suggests that specific design features of Lenti-D LVV likely contributed to this event. The company has shared this information with the independent data monitoring committee of the study and the FDA has placed the eli-cel program on a clinical hold. The company does not anticipate the clinical hold to impact its programs in sickle cell disease (SCD), β-thalassemia or oncology. Subject to resolution of the clinical hold, the company anticipates completing the submission of the rolling BLA for eli-cel in 2021.

"Our hearts go out to this patient and his family, who are dealing with a challenging diagnosis," said Nick Leschly, chief bluebird. "Given what we know, we remain confident that eli-cel can offer hope for patients and families impacted by this devastating disease who have very few treatment options. We are committed to working with regulators and physicians in order to resolve this hold as soon as possible and bring this important therapy to patients in need."

BLUEBIRD BIO BUSINESS UPDATE

Today, bluebird bio is announcing that the company intends to focus its SGD business on the U.S. market and on further investments in research and development to optimize its core three programs in SCD, β-thalassemia and CALD, as well as on the development of a pipeline exploring new disease indications using in vivo LVV technology. The company remains focused and is on track to complete the rolling submissions of the U.S. BLAs in β-thalassemia in 3Q 2021 and CALD in 2021, pending resolution of the eli-cel clinical hold.

In connection with the planned completion of the business separation in the fourth quarter of 2021 and pivot to U.S.-centric efforts for SGD, bluebird plans an orderly wind down of its operations in Europe and to explore how to give patients in Europe access to its gene therapies, including potentially out-licensing the ex-U.S. rights to its three lead products to a company with European experience and capabilities.

"bluebird’s decision to focus on the U.S. market is driven by the challenges of achieving appropriate value recognition and market access for ZYNTEGLO in Europe, which makes bringing its transformative gene therapies like ZYNTEGLO and SKYSONA to patients and physicians in Europe untenable for a small innovative company at this time," said Andrew Obenshain, president, severe genetic diseases, bluebird bio. "While European regulators have been innovative partners in supporting accelerated regulatory paths for these therapies, European payers have not yet evolved their approach to gene therapy in a way that can recognize the innovation and the expected life-long benefit of these products. We are committed to and hope to find a potential partner who can help us carry forward our therapies in Europe."

BLUEBIRD BIO RECENT HIGHLIGHTS

BB1111 AND ZYNTEGLO CLINICAL HOLD LIFT – On June 7, 2021, bluebird announced that the FDA has lifted the clinical holds on the Phase 1/2 HGB-206 and Phase 3 HGB-210 studies of LentiGlobin for SCD gene therapy (bb1111) for adult and pediatric patients with SCD, and the Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies of betibeglogene autotemcel gene therapy (beti-cel; licensed as ZYNTEGLO in the EU and the UK) for adult, adolescent and pediatric patients with transfusion-dependent β-thalassemia (TDT). The company is working closely with study investigators and clinical trial sites to resume all study activities as soon as possible.
β-THALASSEMIA

EHA DATA – On June 11, 2021, bluebird presented data from several studies of beti-cel in adult, adolescent and pediatric patients with TDT. These data were presented during EHA (Free EHA Whitepaper)2021 Virtual, the 26th Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper). With 51 patients enrolled, data from the long-term follow-up study (LTF-303) show that all patients treated with beti-cel who achieve transfusion independence (TI) remain free from transfusions, with the longest follow-up of seven years. Across Phase 3 studies, 89% (32/36) of evaluable patients across ages and genotypes achieved TI and remain transfusion free, including 91% (20/22) of evaluable pediatric patients under the age of 18. Data from bluebird bio’s Phase 1/2 and Phase 3 clinical studies represent more than 220 patient-years of experience with beti-cel.
EU MARKETING AUTHORIZATION – On July 9, 2021, bluebird announced that the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has concluded based on the review of all available data that the benefit-risk balance of ZYNTEGLO (beti-cel) remains favorable. bluebird bio informed the EMA that the company has lifted the voluntary marketing suspension. Today, bluebird is announcing that on the basis of the PRAC decision, the EMA CHMP (Committee for Medicinal Products for Human Use) has endorsed the positive recommendation for ZYNTEGLO by the PRAC. A confirmatory decision by the European Commission (EC) is expected in 3Q 2021.
CEREBRAL ADRENOLEUKODYSTROPHY

SKYSONA EC DECISION – On July 21, 2021, bluebird announced that the EC granted marketing authorization of SKYSONA, a one-time gene therapy for the treatment of early CALD in patients less than 18 years of age with an ABCD1 genetic mutation, and for whom a human leukocyte antigen (HLA)-matched sibling hematopoietic (blood) stem cell (HSC) donor is not available.
2SEVENTY BIO RECENT HIGHLIGHTS

ABECMA LAUNCH – This quarter, bluebird and Bristol-Myers Squibb (BMS) launched ABECMA (idecabtagene vicleucel; ide-cel) in the U.S. ABECMA generated total U.S. revenues of $24 million in 2Q 2021 which bluebird shares equally with BMS. As of June 30, 2021, over 65 sites in the U.S. had been qualified to treat patients. bluebird and BMS have reported robust demand for ABECMA and are working to continue to increase manufacturing capacity over time.
STRATEGIC MANUFACTURING ALLIANCE – On July 28, 2021, bluebird and National Resilience, Inc. (Resilience) announced a strategic alliance aimed to accelerate the early research, development and delivery of cell therapies. As part of the agreement, Resilience will acquire bluebird’s Research Triangle (bRT) manufacturing facility located in North Carolina for $110 million and will retain all of the more than 100 highly skilled technical staff and administrators currently employed at the site. Resilience will continue to support vector supply for both bluebird and 2seventy. The two companies are also finalizing a definitive agreement to establish partner programs that will share expense and revenue for successful commercialized oncology products and in parallel establish a next-generation manufacturing R&D collaboration. Additionally, 2seventy plans to invest in internal drug product manufacturing capability and capacity to support its future clinical studies.
KARMMA ASCO (Free ASCO Whitepaper) DATA – On May 19, 2021, bluebird and BMS announced new data and analyses from the pivotal KarMMa study evaluating ABECMA. These data showed a 24.8-month median overall survival in triple-class exposed relapsed/refractory multiple myeloma. With more than 24-month median follow-up, results represent longest follow-up to date from a global clinical trial of a CAR T cell therapy in multiple myeloma with 73% overall response rate and responses ongoing with a median duration of response in patients achieving a ≥CR of 21.5 months. Analysis of characteristics of neurotoxicity (NT) observed in KarMMa study reinforce well-understood safety profile of ABECMA with mostly Grade 1/2 occurrences of NT having early onset and resolution.
UPCOMING ANTICIPATED MILESTONES

BLUEBIRD BIO

bluebird anticipates the separation of its SGD and oncology businesses into two independent, publicly traded companies (bluebird bio and 2seventy bio) to be completed by the end of 2021.
TDT: The company is on track to complete its rolling BLA submission to the FDA for beti-cel in 3Q 2021. This submission is anticipated to include adult, adolescent and pediatric patients with transfusion dependent β-thalassemia across all genotypes (including non-β0/β0 genotypes and β0/β0 genotypes).
CALD: Subject to resolution of the clinical hold, the company plans to complete its rolling BLA submission to the FDA for eli-cel in 2021.
SCD: The company is continuing to evaluate the impact of the recently-lifted clinical hold on bb1111 and plans to continue to work closely with the FDA in their review of these events to provide an update on the company’s development plan and timeline for submission for regulatory approval of bb1111 by year end.
SCD: The company plans to present clinical data from its ongoing HGB-206 clinical study of bb1111 by the end of 2021.
2SEVENTY BIO

Continued commercial launch of ABECMA in the U.S.
Submission of 1-2 investigational new drug (IND) applications by the end of 2021.
Presentation of clinical data from the ongoing CRB-402 study of bb21217 by the end of 2021.
SECOND QUARTER 2021 FINANCIAL RESULTS

Cash Position: Cash, cash equivalents and marketable securities as of June 30, 2021 and December 31, 2020 were $941.6 million and $1.27 billion, respectively. The decrease in cash, cash equivalents and marketable securities is primarily related to cash used in support of ordinary course operating activities.
Revenues: Total revenues were $7.5 million for the three months ended June 30, 2021 compared to $198.9 million for the three months ended June 30, 2020. Total revenues were $20.3 million for the six months ended June 30, 2021 compared to $220.8 million for the six months ended June 30, 2020. The decrease for both periods was primarily driven by a cumulative catch-up adjustment to revenue recorded in connection with the May 2020 BMS contract modification in the second quarter of 2020.
R&D Expenses: Research and development expenses were $144.3 million for the three months ended June 30, 2021 compared to $156.3 million for the three months ended June 30, 2020. Research and development expenses were $298.8 million for the six months ended June 30, 2021 compared to $310.4 million for the six months ended June 30, 2020. The decrease for both periods was primarily driven by decreased manufacturing expenses, a decrease in license and milestone fees, and a decrease in clinical costs in light of safety events in the HGB-206 study of LentiGlobin for SCD gene therapy.
SG&A Expenses: Selling, general and administrative expenses were $78.6 million for the three months ended June 30, 2021 compared to $68.6 million for the three months ended June 30, 2020. Selling, general and administrative expenses were $165.5 million for the six months ended June 30, 2021 compared to $141.9 million for the six months ended June 30, 2020. The increase for both periods was primarily driven by an increase in consulting fees associated with the ongoing project to separate the company’s severe genetic disease and oncology businesses into two independently traded companies as well as an increased employee compensation, benefit, and other headcount related expenses.
Net Loss: Net loss was $241.7 million for the three months ended June 30, 2021 compared to $21.5 million for the three months ended June 30, 2020. Net loss was $447.5 million for the six months ended June 30, 2021 compared to $224.1 million for the six months ended June 30, 2020.
Investor Conference Call Information

bluebird will hold a conference call to discuss this update on Monday, August 9 at 8:00 a.m. ET. Investors may listen to the call by dialing (844) 825-4408 from locations in the United States or +1 (315) 625-3227 from outside the United States. Please refer to conference ID number 9698691.

To access the live webcast of bluebird’s presentation, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird website at View Source A replay of the webcast will be available on the bluebird website for 90 days following the event.

On August 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 second quarter and first half-year ended June 30, 202 (Press release, BioNTech, AUG 9, 2021, View Source [SID1234586077])1.

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"We and our partner Pfizer have crossed the one billion mark for COVID-19 vaccine doses shipped worldwide. We are proud to have reached this great milestone after only six months and to have made a difference for people with our proprietary mRNA technology. To address the ongoing pandemic, we are expanding the supply of our COVID-19 vaccine to more than 100 countries and regions worldwide, including enhancing access to low- and middle-income countries," said Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. "At the same time, we further developed our oncology pipeline, including the recent initiation of randomized Phase 2 trials for two FixVac programs. We were able to advance multiple oncology programs across various technology platforms which are now entering later stage testing, providing the potential for introducing a series of product candidates to the market in the coming years."

Second Quarter 2021 and Subsequent Updates

Infectious disease

COVID-19 Vaccine Program – BNT162b2

BNT162b2 clinical development updates

Multiple clinical trials are ongoing to expand access to and authorization of BNT162b2 to additional regions and population groups, such as the studies in children from 6 months to 11 years of age, and in healthy pregnant women.
On April 1, 2021, BioNTech and Pfizer announced updated topline results from the global Phase 3 trial of BNT162b2, which showed high efficacy and no serious safety concerns through up to six months following the second dose. The data were published on the medRxiv preprint server on July 29, 2021.1 Topline efficacy was based on an analysis of 971 confirmed symptomatic cases of COVID-19 observed in the pivotal Phase 3 trial through March 13, 2021. BNT162b2 was 91.2% effective against COVID-19, measured seven days through up to six months after the second dose. The vaccine was also 95.7% effective against severe COVID-19 as defined by the Food and Drug Administration (FDA) as measured seven days after the second dose. Safety data collected demonstrated a favorable safety and tolerability profile. An additional exploratory analysis of 800 trial participants enrolled in South Africa confirmed 100% efficacy against SARS-CoV-2 lineage B.1.351 (Beta variant). These data support previous results from immunogenicity studies published in April 15 demonstrating that BNT162b2 induced a robust neutralizing antibody response to the B.1.351 lineage.2 The updated results have been submitted to the regulatory authorities and are currently under review.
A clinical trial within the global Phase 1/2/3 trial is ongoing which includes: (1) an assessment of the impact of a third dose of BNT162b2 in prolonging immunity against COVID-19 and in protecting against COVID-19 caused by potential newly emerging SARS-CoV-2 variants, and (2) an assessment of a modified, variant-specific version of BNT162b2 that targets the full spike protein of the Beta variant. The aim of these studies is to explore the development, manufacturing, and regulatory pathway that BioNTech and Pfizer would pursue if SARS-CoV-2 were to change enough to require an updated vaccine.
On June 10, 2021, BioNTech and Pfizer published results in Nature from in vitro studies demonstrating that sera from individuals vaccinated with BNT162b2 neutralize the SARS-CoV-2 lineages B.1.617.1 (Delta variant) and B.1.525 (Eta variant, first identified in Nigeria). Neutralization against the Eta variant was comparable to the neutralization against the wild-type virus, whereas the neutralization against the Delta variant was less than that against the wild-type virus, though still efficient.3
In July 2021, BioNTech and Pfizer provided an update on their comprehensive booster strategy. In initial data from the ongoing Phase 1/2/3 booster trial of a third dose of the current BNT162b2 vaccine the companies have observed that a booster dose given six months after the second dose has a consistent tolerability profile while eliciting high neutralization titers in both younger and older adults compared to those observed after two primary doses. The immune sera elicited neutralizing titers against the original SARS-CoV-2 wild-type strain that are more than 5 to 8-fold, and more than 15 to 21-fold against the B.1.351 lineage (Beta variant) than after two primary doses. In addition, a third dose of BNT162b2 elicited neutralizing titers against the Delta variant that are more than 5 to 11-fold than after two doses. The companies expect to publish more definitive data about the analysis and plan to submit the data to the FDA, European Medicines Agency (EMA) and other regulatory authorities in the coming weeks.
While BioNTech and Pfizer believe a third dose of BNT162b2 has the potential to preserve the highest levels of protective efficacy against all currently tested variants, including Delta, the companies are remaining vigilant and are developing and will clinically test an updated version of the COVID-19 vaccine that targets the full spike protein of the Delta variant. This trial, aimed at studying the Delta variant, is part of BioNTech’s and Pfizer’s comprehensive strategy to address variants should the need arise in the future. The companies anticipate the clinical study to begin in August 2021, subject to regulatory approvals.

In July 2021, BioNTech and Pfizer began a Phase 3 clinical trial to evaluate the safety, tolerability and efficacy of a 30µg booster dose of BNT162b2 versus placebo in approximately 10,000 participants aged 16 years and older who have previously received two doses of BNT162b2 at least six months prior to randomization. Participants will be followed for up to twelve months. The trial is being conducted in the United States, Brazil and South Africa.
Regulatory updates

In May 2021, BioNTech and Pfizer announced the expansion of emergency use authorizations, conditional marketing authorizations or equivalent for adolescents 12 years of age and older in the United States, European Union and Canada. Authorizations for adolescents 12 years of age and older have also been granted in additional countries.
On May 17, 2021, BioNTech announced that the FDA and the EMA approved the transportation and storage of thawed, undiluted vials of BNT162b2 at fridge temperatures of 2°C to 8°C for up to one month (31 days).
On July 16, 2021, the FDA granted Priority Review designation for the Biologics License Application (BLA) for BNT162b2 to prevent COVID-19 in individuals 16 years of age and older. This follows the completion of the rolling submission of the BLA in May 2021, which includes data from the pivotal Phase 3 clinical trial of the vaccine. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in January 2022. Additional submissions to pursue regulatory approvals in those countries where emergency use authorizations or equivalents were initially granted are ongoing or planned.

Commercial updates

As of July 21, 2021, BioNTech and Pfizer have shipped approximately one billion doses of BNT162b2 to more than 100 countries or territories around the world.
The companies have signed orders of more than 2.2 billion doses for delivery in 2021 and more than one billion doses for 2022 and beyond as of July 21, 2021. Further discussions for additional dose commitments are ongoing and the order book is expected to further grow.

On May 20, 2021, BioNTech and Pfizer announced an agreement with the European Commission (EC) to supply 900 million doses to the European Union, with an option for the EC to request up to an additional 900 million doses. This brings the total number of potential doses delivered to the EC, inclusive of all agreements, to up to 2.4 billion. The EC also has the option to purchase an updated version of the vaccine that includes new formulations or addresses potential viral variants, if available and approved. All doses for the EC are planned to be manufactured in the European Union.
On June 10, 2021, BioNTech and Pfizer announced plans to provide the U.S. government with 500 million doses at a not-for-profit price, of which 200 million doses will be provided in 2021 and 300 million doses will be provided in the first half of 2022. The U.S. government will donate vaccine doses to low- and lower middle-income countries and organizations that support them. These doses are part of BioNTech’s and Pfizer’s previously announced pledge to provide two billion doses of the COVID-19 vaccine to low- and middle-income countries over the next 18 months.
On July 23, 2021, BioNTech and Pfizer announced that the U.S. government purchased an additional 200 million doses, bringing the total number of doses under the existing supply agreement to 500 million. The companies expect to deliver 110 million of the additional doses by December 31, 2021, and the remaining 90 million doses no later than April 20, 2022. The U.S. government also has the option to acquire an updated version of the vaccine that includes new formulations or addresses potential viral variants, if available and authorized.
Manufacturing Updates

BioNTech and Pfizer expect BNT162b2 annual manufacturing capacity to reach three billion doses by the end of 2021 and expect to have capacity to manufacture up to four billion doses in 2022.
In the second quarter of 2021, the EMA approved the manufacturing of BioNTech’s COVID-19 vaccine drug product at its facility in Marburg, Germany. This manufacturing facility is one of the largest mRNA vaccine manufacturing sites worldwide with an annual production capacity of up to one billion doses of COVID-19 vaccine, once fully operational. The first batches of vaccines manufactured at the Marburg facility were delivered in mid-April 2021.
On May 10, 2021, BioNTech announced plans to establish a fully-integrated mRNA manufacturing facility in Singapore with support from the Singapore Economic Development Board (EDB), as well as plans to establish its first regional headquarters for South East Asia. The new facility will leverage cutting-edge manufacturing and digital infrastructure and will be equipped to produce a range of novel mRNA vaccines and therapeutics. The envisioned site will bring highly automated and end-to-end mRNA production capabilities. The facility, with an estimated annual capacity of several hundred million doses, will provide regional and global supply capacity, as well as a rapid response capability for South East Asia to address potential pandemic threats. BioNTech anticipates the site could be operational as early as 2023.
On July 21, 2021, BioNTech and Pfizer announced the signing of a letter of intent with The Biovac Institute (Pty) Ltd. ("Biovac"), a Cape Town-based, South African biopharmaceutical company, for the manufacture of vaccine for distribution within the African Union. Biovac will perform fill and finish manufacturing and distribution activities within BioNTech’s and Pfizer’s global COVID-19 vaccine supply chain and manufacturing network. Biovac’s Cape Town facility is expected to be incorporated into the vaccine supply chain by the end of 2021. At full operational capacity, the annual production will exceed 100 million finished doses annually. All doses will exclusively be distributed within the 55-member states that make up the African Union.
Influenza Vaccine Program – BNT161

BNT161 – A Phase 1 clinical trial is expected to start in the third quarter of 2021. The clinical trial will evaluate modified RNA influenza vaccine candidates based on the proven BNT162b2 COVID-19 vaccine platform. BNT161 is partnered with Pfizer.

Malaria Vaccine Program

On July 26, 2021, BioNTech announced plans to develop sustainable solutions to address infectious diseases on the African continent. As part of the plans, BioNTech aims to develop a well-tolerated and highly effective Malaria vaccine, beginning with the initiation of a clinical trial by end of 2022. BioNTech will assess multiple vaccine candidates featuring known targets such as circumsporozoite protein (CSP) as well as new antigens discovered in the pre-clinical research phase. The second objective is dedicated to the development of sustainable vaccine production and supply solutions on the African continent. To this end, BioNTech is exploring possibilities to set up state-of-the-art mRNA manufacturing facilities, either with partners or on its own. This strategy aims to expand the capacity of low- and middle-income countries to manufacture contemporary vaccines end-to-end and scale up production to increase global access. BioNTech’s efforts are supported by the World Health Organization and the Africa Centers for Disease Control and Prevention. Besides the WHO, the European Commission and other organizations have been involved in the early planning phase of BioNTech’s Malaria project and have offered their support to identify and set up the necessary infrastructure. BioNTech’s Malaria project is part of the ‘eradicateMalaria’ initiative, led by the kENUP Foundation, to accelerate the eradication of Malaria.

Oncology

BioNTech is accelerating the development of a broad oncology pipeline which has now advanced 15 product candidates in 18 ongoing trials. Six clinical trials, including two randomized Phase 2 clinical trials for FixVac programs, BNT111 and BNT113, have started in 2021. In the second quarter of 2021, the Company started first-in-human Phase 1 trials for the neoantigen specific T cell therapy, BNT221, and for a second RiboCytokine program, BNT152+153. BioNTech expects to further advance its oncology pipeline in the second half of 2021 with BNT122 expected to move into a randomized Phase 2 trial, and two further preclinical programs to move into Phase 1 trials.
During the remainder of 2021, BioNTech expects at least four data updates from its ongoing clinical trials in oncology.

mRNA programs

FixVac

BNT111 – On June 18, 2021, BioNTech announced that the first patient was dosed in a randomized global, three-arm Phase 2 trial evaluating BNT111 in combination with cemiplimab versus both agents as monotherapy, in patients with anti-PD1-refractory/relapsed unresectable Stage III or IV melanoma. Melanoma remains one of the deadliest types of skin cancer with a 5-year survival for Stage IV metastatic disease of only 22.5%. In the refractory or relapsed setting, survival can be as short as six months depending on risk factors. Up to 50% of patients progress after treatment with checkpoint inhibitors.
The open-label randomized trial is expected to enroll a total of 120 patients. The primary endpoint is overall response rate of BNT111 in combination with cemiplimab. Secondary endpoints include overall response rate in the single agent arms, duration of response, and safety.

BNT113 – Today, BioNTech announced that the first patient was dosed in July 2021 in a potentially registrational 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. HPV-associated cancers are increasing, with HPV16+ HNSCC typically occurring in younger people. Most patients with HPV16+ HNSCC are diagnosed at more advanced clinical stages. BioNTech sees a significant opportunity to improve the treatment landscape with BNT113 given that it has the potential to augment clinical responses in patients being treated with checkpoint inhibitors.
BNT113 has not previously been combined with anti-PD1 therapy, and the Phase 2 trial will start with a run-in portion (Part A) designed to demonstrate the safety of the combination of BNT113 and pembrolizumab. After approximately 12 to 18 patients have completed one cycle, safety and recommended Phase 2 dosage will be confirmed, and assuming clinical success, the trial will be advanced to Part B.
Part B is planned to enroll a total of 267 patients. Primary endpoints include safety, overall survival and objective response rate. Secondary endpoints include progression free survival, durable complete responses, duration of response, patient reported outcomes and quality of life measures.

BNT114 – The main study phase of BNT114 Phase 1 in triple negative breast cancer (TNBC-MERIT) was completed and recently summarized in a clinical trial report. A long-term follow-up period is ongoing until 2023 for patients receiving the individualized neoantigen specific vaccine only. Treatment with an on demand manufactured BNT114-vaccine was feasible in terms of timelines, logistics, and patient burden in a standard clinical healthcare setting. Main study data demonstrated that treatment with BNT114 had an acceptable safety and tolerability profile, which was in line with the known mode of action and was accompanied by transient increases in cytokine levels.
Individualized neoantigen specific immunotherapy (iNeST)

BNT122 (Autogene Cevumeran) – BioNTech’s iNeST product candidate is partnered with Genentech. Dosing of the first patient in the randomized Phase 2 trial in the adjuvant treatment of circulating tumor DNA positive, surgically resected Stage II (high risk)/Stage III colorectal cancer is planned for the second half of 2021. The trial is currently recruiting patients.
RiboCytokines

BNT152+153 – In June 2021 the first patient was dosed in a first-in-human Phase 1 trial evaluating a combination of BNT152 (encoding IL-7) and BNT153 (encoding IL-2). The trial will enroll approximately 72 patients with various solid tumors. In parallel, BNT152 and BNT153 monotherapy dose escalation in Part 1 will determine the Part 2 dose of each compound. Part 2 will be the dose escalation of BNT152 and BNT153 in combination.
RiboMabs

BNT141 – BioNTech plans to start a Phase 1 clinical trial for BNT141 in the second half of 2021.
BNT142 – BioNTech plans to start a Phase 1 clinical trial for BNT142 in the second half of 2021.
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 1/2a dose escalation trial with multiple expansion cohorts in patients with solid tumors is ongoing. A data update for the trial is planned in the second half of 2021.
BNT312/GEN1042 – A Phase 1/2a dose escalation trial with multiple expansion cohorts in patients with solid tumors is ongoing. The first data disclosure for the trial is planned in the second half of 2021.
Cell therapies

CAR-T cell immunotherapy

BNT211 – A first-in-human Phase 1/2a open-label dose escalation and dose expansion trial evaluating BNT211 in patients with Claudin-6-positive solid tumors is ongoing. The trial evaluates Claudin-6 CAR-T cells dosed as monotherapy and in combination with Claudin-6 CARVac. A data update for this trial is planned in the second half of 2021.
Neoantigen-targeting T cell therapy

BNT221 – In April 2021, the first patient was dosed in a first-in-human Phase 1 dose escalation trial evaluating BNT221 in patients with checkpoint inhibitor unresponsive or refractory metastatic melanoma. Part 1 of the trial consists of a monotherapy dose escalation of BNT221. In Part 2, BNT221 will be dosed in combination with anti-PD1 therapy after first-line treatment.
Small molecule immunomodulators

Toll-like receptor binding agonist

BNT411 – A Phase 1/2a 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. A data update from this trial is planned in the second half of 2021.
Corporate Updates

On July 19, 2021, BioNTech and Kite Pharma, a Gilead company, announced the companies have entered into a purchase agreement for BioNTech to acquire Kite’s solid tumor neoantigen T cell receptor (TCR) R&D platform and clinical manufacturing facility in Gaithersburg, MD. The acquired facility will provide production capacity to support clinical trials in the United States and will complement BioNTech’s existing cell therapy manufacturing facility in Idar-Oberstein, Germany. The facility will also support the development of BioNTech’s expanding pipeline of novel cell therapies. Under the terms of the agreement, Kite received a one-time upfront payment from BioNTech. The asset acquisition closed on August 4, 2021 and is an important step in the BioNTech’s goal to build a global biotechnology company for individualized cancer medicine. The acquisition further strengthens the Company’s footprint in the United States.
Management Updates

On May 18, 2021, BioNTech announced that Jens Holstein was appointed to the Management Board as Chief Financial Officer. Jens Holstein joined the Management Board on July 1, 2021 to help strengthen BioNTech on its growth trajectory as a global, fully integrated immunotherapy company. Jens Holstein takes over the CFO role from Dr. Sierk Poetting who will fully focus on his tasks as Chief Operating Officer (COO).
Second Quarter 2021 Financial Results (unaudited)

Revenues: Total revenues were estimated to be €5,308.5 million4 for the three months ended June 30, 2021, compared to €41.7 million for the three months ended June 30, 2020. For the six months ended June 30, 2021, total revenues were estimated to be €7,356.9 million4 compared to €69.4 million for the comparative prior year period. The increase was mainly due to rapid increases in the supply of 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 June 30, 2021, BioNTech’s commercial revenues included an estimated amount of €3,923.7 million4 gross profit share and €168.6 million of sales milestones. During the six months ended June 30, 2021, BioNTech’s commercial revenues included an estimated amount of €5,428.4 million4 gross profit share and €415.8 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 six months ended June 30, 2021, respectively, €138.1 million and €202.0 million sales to BioNTech’s collaboration partners of products manufactured by BioNTech as well as €1,035.6 million and €1,235.4 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 €883.8 million4 for the three months ended June 30, 2021, compared to €5.6 million for the three months ended June 30, 2020. For the six months ended June 30, 2021, cost of sales were estimated to be €1,116.9 million4, compared to €11.5 million for the comparative prior year period. During the three and six months ended June 30, 2021, estimated cost of sales of €872.1 million4 and €1,095.3 million4, 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 €201.1 million for the three months ended June 30, 2021, compared to €95.2 million for the three months ended June 30, 2020. For the six months ended June 30, 2021, research and development expenses were €417.3 million, compared to €160.3 million for the comparative prior year period. The increase was mainly due to an increase in research and development expenses for BioNTech’s BNT162 program, recorded as purchased services with respect to those expenses, which were initially incurred by Pfizer and subsequently charged to BioNTech under the collaboration agreement. The increase was further driven by an increase in wages, benefits and social security expenses due to increases in headcounts, recognizing inventor compensation expenses as well as expenses incurred under the new share-based-payment arrangements.

General and Administrative Expenses: General and administrative expenses were €47.8 million for the three months ended June 30, 2021, compared to €18.8 million for the three months ended June 30, 2020. For the six months ended June 30, 2021, general and administrative expenses were €86.7 million, compared to €34.6 million for the comparative prior year period. The increase was mainly due to an increase in wages, benefits and social security expenses from increasing headcounts and recognizing expenses incurred under the new share-based-payment arrangements, higher expenses for purchased management consulting and legal services, as well as higher insurance premiums.
Income Taxes: Interim income taxes were €1,235.6 million and €1,749.8 million for the three and six months ended June 30, 2021, respectively, and were recognized using the estimated annual effective income tax rate of approximately 31%.

Net Profit/(Loss): Net profit was €2,787.2 million for the three months ended June 30, 2021, compared to €88.3 million net loss for the three months ended June 30, 2020. For the six months ended June 30, 2021, net profit was €3,915.3 million, compared to €141.7 million net loss for the comparative prior year period.

Cash Position: Cash and cash equivalents as of June 30, 2021 were €914.1 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, trade receivables which were outstanding as of June 30, 2021 were received as payments in July 2021, improving BioNTech’s cash position.

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

Update on current signed COVID-19 vaccine order book for the 2021 financial year:

Estimated COVID-19 vaccine revenues to BioNTech for the 2021 financial year upon delivery of currently signed supply contracts of ~2.2 billion doses as of July 21, 2021 is ~€15.9 billion5.

This revenue estimate reflects:

Expected revenues from direct COVID-19 vaccine sales to customers in BioNTech’s territory
Expected revenues from sales to collaboration partners of products manufactured by BioNTech
Expected sales milestone payments from collaboration partners
Expected revenues related to share of gross profit from COVID-19 vaccine sales in the collaboration partners’ territories

Additional revenues related to further supply contracts for deliveries in 2021 expected with first contracts already in place for 2022 and beyond.

Full year 2021 manufacturing capacity targeting 3 billion doses and up to 4 billion doses for the year 2022.
Update on 2021 Financial Outlook:

Planned Full Year 2021 Expenses and Capex5
R&D expenses €950 million – €1,050 million
Ramp-up of R&D investment in the second half of 2021 planned
to expand and accelerate the pipeline development
SG&A expenses €250 million – €300 million
Capital expenditures €175 million – €225 million
Estimated Full Year 2021 Tax Assumptions
BioNTech Group estimated annual effective income tax rate ~31%
The full interim unaudited condensed consolidated financial statements can be found in BioNTech’s Quarterly Report on Form 6-K, filed today with the SEC and available at View Source

1Thomas SJ et al.. Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine; medRxiv Preprint, July 29, 2021. Available at View Source
2N Engl J Med.. Neutralizing Activity of BNT162b2-Elicited Serum; 2021 Apr 15;384(15):1466-1468. Available at View Source
3Nature. BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants; 2021 Jun 10. Online ahead of print.. Available at: View Source
4Estimated 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 Six Months Ended June 30, 2021, which is 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.
5Figures have been estimated at constant foreign exchange rates and reflect current base case projections.

On August 9, 2021 bluebird bio, Inc. (NASDAQ: BLUE) reported financial results and business highlights for the second quarter ended June 30, 2021 and provided operational updates, including the announcement that the U.S. Food and Drug Administration (FDA) placed a clinical hold on clinical studies of elivaldogene autotemcel (eli-cel, Lenti-D) gene therapy (licensed as SKYSONA in Europe) for cerebral adrenoleukodystrophy (CALD) (Press release, bluebird bio, AUG 9, 2021, View Source [SID1234586076]).

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"I’m tremendously proud of what bluebird has accomplished this quarter both operationally and strategically to ready ourselves to launch both bluebird bio and 2seventy bio," said Nick Leschly, chief bluebird. "Seven months after announcing our intent to split, and thanks to the incredibly hard work by our teams, we have created a solid foundation for both organizations. The ABECMA launch is exceeding expectations, the oncology INDs and severe genetic disease (SGD) biologics license application (BLA) filings are tracking for later this year, and we have established clear visions and leadership teams for each business. Importantly, we have made tough strategic decisions to reshape the overall cost structure to allow both companies to launch in a strong position to execute through important value-creating milestones."

BUSINESS SEPARATION

In January 2021, bluebird announced its intent to separate into two independent, publicly traded companies (bluebird bio and 2seventy bio). The company expects the separation to be completed by the end of 2021 and to be tax-free to bluebird shareholders.

Key members of the executive teams of both companies have been announced, effective upon completion of the planned separation. This includes Andrew Obenshain as CEO of bluebird and Nick Leschly as CEO of 2seventy.
The full board of directors for both companies will be announced closer to the separation date.
2seventy has confidentially filed its Form 10 Registration Statement with the U.S. Securities and Exchange Commission (SEC), in which it describes the planned tax-free spin-off of 2seventy as a publicly traded company.
bluebird plans to distribute 100% of the outstanding shares of 2seventy common stock to bluebird’s stockholders on a pro-rata basis.
Based on current cash position and the expected $110M upfront payment upon closing of the National Resilience, Inc. strategic collaboration, the Company anticipates having a cash balance of approximately $900M at the time of separation. Together with existing and emerging sources of revenue, we expect our cash balance will be sufficient to fund approximately 24 months of operations for bluebird and 2seventy under current business plans.
ELI-CEL SAFETY UPDATE

The company received a reported Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS), that is likely mediated by Lenti-D lentiviral vector (LVV) insertion, in a patient who was treated with eli-cel, or Lenti-D drug product for CALD over one year ago in the Phase 3 ALD-104 study. Evidence currently available suggests that specific design features of Lenti-D LVV likely contributed to this event. The company has shared this information with the independent data monitoring committee of the study and the FDA has placed the eli-cel program on a clinical hold. The company does not anticipate the clinical hold to impact its programs in sickle cell disease (SCD), β-thalassemia or oncology. Subject to resolution of the clinical hold, the company anticipates completing the submission of the rolling BLA for eli-cel in 2021.

"Our hearts go out to this patient and his family, who are dealing with a challenging diagnosis," said Nick Leschly, chief bluebird. "Given what we know, we remain confident that eli-cel can offer hope for patients and families impacted by this devastating disease who have very few treatment options. We are committed to working with regulators and physicians in order to resolve this hold as soon as possible and bring this important therapy to patients in need."

BLUEBIRD BIO BUSINESS UPDATE

Today, bluebird bio is announcing that the company intends to focus its SGD business on the U.S. market and on further investments in research and development to optimize its core three programs in SCD, β-thalassemia and CALD, as well as on the development of a pipeline exploring new disease indications using in vivo LVV technology. The company remains focused and is on track to complete the rolling submissions of the U.S. BLAs in β-thalassemia in 3Q 2021 and CALD in 2021, pending resolution of the eli-cel clinical hold.

In connection with the planned completion of the business separation in the fourth quarter of 2021 and pivot to U.S.-centric efforts for SGD, bluebird plans an orderly wind down of its operations in Europe and to explore how to give patients in Europe access to its gene therapies, including potentially out-licensing the ex-U.S. rights to its three lead products to a company with European experience and capabilities.

"bluebird’s decision to focus on the U.S. market is driven by the challenges of achieving appropriate value recognition and market access for ZYNTEGLO in Europe, which makes bringing its transformative gene therapies like ZYNTEGLO and SKYSONA to patients and physicians in Europe untenable for a small innovative company at this time," said Andrew Obenshain, president, severe genetic diseases, bluebird bio. "While European regulators have been innovative partners in supporting accelerated regulatory paths for these therapies, European payers have not yet evolved their approach to gene therapy in a way that can recognize the innovation and the expected life-long benefit of these products. We are committed to and hope to find a potential partner who can help us carry forward our therapies in Europe."

BLUEBIRD BIO RECENT HIGHLIGHTS

BB1111 AND ZYNTEGLO CLINICAL HOLD LIFT – On June 7, 2021, bluebird announced that the FDA has lifted the clinical holds on the Phase 1/2 HGB-206 and Phase 3 HGB-210 studies of LentiGlobin for SCD gene therapy (bb1111) for adult and pediatric patients with SCD, and the Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies of betibeglogene autotemcel gene therapy (beti-cel; licensed as ZYNTEGLO in the EU and the UK) for adult, adolescent and pediatric patients with transfusion-dependent β-thalassemia (TDT). The company is working closely with study investigators and clinical trial sites to resume all study activities as soon as possible.
β-THALASSEMIA

EHA DATA – On June 11, 2021, bluebird presented data from several studies of beti-cel in adult, adolescent and pediatric patients with TDT. These data were presented during EHA (Free EHA Whitepaper)2021 Virtual, the 26th Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper). With 51 patients enrolled, data from the long-term follow-up study (LTF-303) show that all patients treated with beti-cel who achieve transfusion independence (TI) remain free from transfusions, with the longest follow-up of seven years. Across Phase 3 studies, 89% (32/36) of evaluable patients across ages and genotypes achieved TI and remain transfusion free, including 91% (20/22) of evaluable pediatric patients under the age of 18. Data from bluebird bio’s Phase 1/2 and Phase 3 clinical studies represent more than 220 patient-years of experience with beti-cel.
EU MARKETING AUTHORIZATION – On July 9, 2021, bluebird announced that the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has concluded based on the review of all available data that the benefit-risk balance of ZYNTEGLO (beti-cel) remains favorable. bluebird bio informed the EMA that the company has lifted the voluntary marketing suspension. Today, bluebird is announcing that on the basis of the PRAC decision, the EMA CHMP (Committee for Medicinal Products for Human Use) has endorsed the positive recommendation for ZYNTEGLO by the PRAC. A confirmatory decision by the European Commission (EC) is expected in 3Q 2021.
CEREBRAL ADRENOLEUKODYSTROPHY

SKYSONA EC DECISION – On July 21, 2021, bluebird announced that the EC granted marketing authorization of SKYSONA, a one-time gene therapy for the treatment of early CALD in patients less than 18 years of age with an ABCD1 genetic mutation, and for whom a human leukocyte antigen (HLA)-matched sibling hematopoietic (blood) stem cell (HSC) donor is not available.
2SEVENTY BIO RECENT HIGHLIGHTS

ABECMA LAUNCH – This quarter, bluebird and Bristol-Myers Squibb (BMS) launched ABECMA (idecabtagene vicleucel; ide-cel) in the U.S. ABECMA generated total U.S. revenues of $24 million in 2Q 2021 which bluebird shares equally with BMS. As of June 30, 2021, over 65 sites in the U.S. had been qualified to treat patients. bluebird and BMS have reported robust demand for ABECMA and are working to continue to increase manufacturing capacity over time.
STRATEGIC MANUFACTURING ALLIANCE – On July 28, 2021, bluebird and National Resilience, Inc. (Resilience) announced a strategic alliance aimed to accelerate the early research, development and delivery of cell therapies. As part of the agreement, Resilience will acquire bluebird’s Research Triangle (bRT) manufacturing facility located in North Carolina for $110 million and will retain all of the more than 100 highly skilled technical staff and administrators currently employed at the site. Resilience will continue to support vector supply for both bluebird and 2seventy. The two companies are also finalizing a definitive agreement to establish partner programs that will share expense and revenue for successful commercialized oncology products and in parallel establish a next-generation manufacturing R&D collaboration. Additionally, 2seventy plans to invest in internal drug product manufacturing capability and capacity to support its future clinical studies.
KARMMA ASCO (Free ASCO Whitepaper) DATA – On May 19, 2021, bluebird and BMS announced new data and analyses from the pivotal KarMMa study evaluating ABECMA. These data showed a 24.8-month median overall survival in triple-class exposed relapsed/refractory multiple myeloma. With more than 24-month median follow-up, results represent longest follow-up to date from a global clinical trial of a CAR T cell therapy in multiple myeloma with 73% overall response rate and responses ongoing with a median duration of response in patients achieving a ≥CR of 21.5 months. Analysis of characteristics of neurotoxicity (NT) observed in KarMMa study reinforce well-understood safety profile of ABECMA with mostly Grade 1/2 occurrences of NT having early onset and resolution.
UPCOMING ANTICIPATED MILESTONES

BLUEBIRD BIO

bluebird anticipates the separation of its SGD and oncology businesses into two independent, publicly traded companies (bluebird bio and 2seventy bio) to be completed by the end of 2021.
TDT: The company is on track to complete its rolling BLA submission to the FDA for beti-cel in 3Q 2021. This submission is anticipated to include adult, adolescent and pediatric patients with transfusion dependent β-thalassemia across all genotypes (including non-β0/β0 genotypes and β0/β0 genotypes).
CALD: Subject to resolution of the clinical hold, the company plans to complete its rolling BLA submission to the FDA for eli-cel in 2021.
SCD: The company is continuing to evaluate the impact of the recently-lifted clinical hold on bb1111 and plans to continue to work closely with the FDA in their review of these events to provide an update on the company’s development plan and timeline for submission for regulatory approval of bb1111 by year end.
SCD: The company plans to present clinical data from its ongoing HGB-206 clinical study of bb1111 by the end of 2021.
2SEVENTY BIO

Continued commercial launch of ABECMA in the U.S.
Submission of 1-2 investigational new drug (IND) applications by the end of 2021.
Presentation of clinical data from the ongoing CRB-402 study of bb21217 by the end of 2021.
SECOND QUARTER 2021 FINANCIAL RESULTS

Cash Position: Cash, cash equivalents and marketable securities as of June 30, 2021 and December 31, 2020 were $941.6 million and $1.27 billion, respectively. The decrease in cash, cash equivalents and marketable securities is primarily related to cash used in support of ordinary course operating activities.
Revenues: Total revenues were $7.5 million for the three months ended June 30, 2021 compared to $198.9 million for the three months ended June 30, 2020. Total revenues were $20.3 million for the six months ended June 30, 2021 compared to $220.8 million for the six months ended June 30, 2020. The decrease for both periods was primarily driven by a cumulative catch-up adjustment to revenue recorded in connection with the May 2020 BMS contract modification in the second quarter of 2020.
R&D Expenses: Research and development expenses were $144.3 million for the three months ended June 30, 2021 compared to $156.3 million for the three months ended June 30, 2020. Research and development expenses were $298.8 million for the six months ended June 30, 2021 compared to $310.4 million for the six months ended June 30, 2020. The decrease for both periods was primarily driven by decreased manufacturing expenses, a decrease in license and milestone fees, and a decrease in clinical costs in light of safety events in the HGB-206 study of LentiGlobin for SCD gene therapy.
SG&A Expenses: Selling, general and administrative expenses were $78.6 million for the three months ended June 30, 2021 compared to $68.6 million for the three months ended June 30, 2020. Selling, general and administrative expenses were $165.5 million for the six months ended June 30, 2021 compared to $141.9 million for the six months ended June 30, 2020. The increase for both periods was primarily driven by an increase in consulting fees associated with the ongoing project to separate the company’s severe genetic disease and oncology businesses into two independently traded companies as well as an increased employee compensation, benefit, and other headcount related expenses.
Net Loss: Net loss was $241.7 million for the three months ended June 30, 2021 compared to $21.5 million for the three months ended June 30, 2020. Net loss was $447.5 million for the six months ended June 30, 2021 compared to $224.1 million for the six months ended June 30, 2020.
Investor Conference Call Information

bluebird will hold a conference call to discuss this update on Monday, August 9 at 8:00 a.m. ET. Investors may listen to the call by dialing (844) 825-4408 from locations in the United States or +1 (315) 625-3227 from outside the United States. Please refer to conference ID number 9698691.

To access the live webcast of bluebird’s presentation, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird website at View Source A replay of the webcast will be available on the bluebird website for 90 days following the event.

On August 9, 2021 Seagen Inc. (Nasdaq: SGEN), a world leader and pioneer in antibody-drug conjugate (ADC) therapies, and RemeGen Co., Ltd. (9995.HK), a leading innovative biopharmaceutical company in China, reported that the two companies have entered into an exclusive worldwide licensing agreement to develop and commercialize disitamab vedotin, a novel HER2-targeted ADC (Press release, Seagen, AUG 9, 2021, View Source [SID1234586075]).

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Disitamab vedotin combines the drug-linker technology originally developed by Seagen with RemeGen’s novel HER2 antibody exhibiting higher affinity and an increased internalization rate as compared to trastuzumab in preclinical models.1, 2 As monotherapy, disitamab vedotin has demonstrated antitumor activity in clinical trials in several solid tumor types, including urothelial, gastric and breast cancer, as well as across a spectrum of HER2 expression levels. In addition, promising combination activity was demonstrated with a PD-1 inhibitor in urothelial cancer.3 It is believed that vedotin-based immunogenic cell death (ICD) may differentiate this class of ADC’s when combined with checkpoint inhibitors.

"This collaboration leverages Seagen’s world-class expertise and knowledge of ADC development, manufacturing and commercialization to maximize the potential of disitamab vedotin. It also complements our existing franchises and our deep and diverse portfolio of innovative anti-cancer therapies for patients in need," said Clay Siegall, Ph.D., President and CEO, Seagen. "The addition of disitamab vedotin as a late-stage asset with multiple development opportunities aligns strategically with our plans to continue expanding our global footprint and deliver meaningful therapies to patients around the world."

Disitamab vedotin received U.S. Food and Drug Administration (FDA) Breakthrough Therapy designation in 2020 for use in second-line treatment of patients with HER2-expressing, locally advanced or metastatic urothelial cancer (mUC) who have previously received platinum-containing chemotherapy. In the same year, RemeGen announced FDA’s clearance of an Investigational New Drug (IND) application for a Phase II clinical trial in mUC. Disitamab vedotin is conditionally approved for treating locally advanced metastatic gastric cancer in China, and in July 2021 the National Medical Products Administration (NMPA) of China also accepted a New Drug Application for disitamab vedotin in mUC.

"Disitamab vedotin has demonstrated robust antitumor activity in multiple advanced cancers where no effective therapy is available," said Jianmin Fang, Ph.D., Co-founder, CEO and CSO, RemeGen. "Seagen is a well-known global biotechnology company recognized for its capabilities in the field of oncology and ADC therapies. We are delighted to partner with Seagen to maximize the potential of disitamab vedotin and to make it available to patients worldwide. We believe this license agreement highlights the global potential of disitamab vedotin in the ADC arena and is a major milestone for us as we begin the journey to transform from a domestic to a global biopharmaceutical company."

Under the terms of the agreement, Seagen will make a $200 million upfront payment to exclusively license rights to disitamab vedotin for global development and commercialization, outside of RemeGen’s territory. RemeGen will retain development and commercialization rights for Asia, excluding Japan and Singapore. Seagen will lead global development and RemeGen will fund and operationalize the portion of global clinical trials attributable to its territory. RemeGen will also be responsible for all clinical development and regulatory submissions specific to its territory.

Seagen will pay RemeGen up to $2.4 billion in potential total milestone payments based upon the achievement of specified development, regulatory and commercialization goals across multiple indications and products. RemeGen will be entitled to a tiered, high single digit to mid-teen percentage royalty based on net sales of disitamab vedotin in Seagen’s territory.

About Disitamab Vedotin (RC48)

Disitamab vedotin is a novel ADC that selectively delivers the anti-cancer agent monomethyl auristatin E (MMAE) into HER2-expressing tumor cells. The novel antibody component of the ADC exhibits a higher affinity and increased internalization rate as compared to trastuzumab in preclinical models, and in animal models, demonstrates promising antitumor activity. It is the first domestically developed ADC in China to receive marketing approval. In June 2021, disitamab vedotin received conditional approval by the NMPA of China to treat locally advanced or metastatic gastric cancer (GEJ carcinoma). In July 2021, the NMPA accepted the New Drug Application for disitamab vedotin in locally advanced or metastatic urothelial carcinoma. In addition, disitamab vedotin has shown significant antitumor activity in clinical trials of a number of HER2-expressing cancers, including those with low HER2 expression. It is currently being studied in multiple late-stage clinical trials across several solid tumor types.

On August 9, 2021 Prescient Therapeutics’ (ASX: PTX) reported that strong cash position will enable it to advance its multiple cancer programs, with work to follow on from what managing director Steven Yatomi-Clarke describes as "tremendous" FY 2021 (Press release, Prescient Therapeutics, AUG 9, 2021, View Source;utm_medium=rss&utm_campaign=after-tremendous-fy-2021-prescient-therapeutics-well-funded-to-advance-cancer-fighting-therapies [SID1234586069]).

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The company develops personalised medicinal approaches to cancer, including targeted and cellular therapies.

Its targeted therapy candidates PTX-100 and PTX-200 are designed to inhibit cancer growth and tumour survival, while OmniCAR is a universal immune receptor platform being developed for next-generation CAR-T therapies for acute myeloid leukemia, HER2-positive solid tumours including breast, ovarian and gastric cancers, and glioblastoma multiforme (brain cancer).

Prescient ended the June quarter with $16.1 million cash in the bank after spending $280,000 on research and development activities in Australia and the United States, particularly related to the development of OmniCAR and cell therapy enhancements, and the ongoing clinical studies of PTX-100 and PTX-200.

Recent accomplishments include successful results from a phase 1b trial of PTX-100, announced after 30 June, which has led to an expanded study of the drug candidate to treat T cell lymphoma, and trial and manufacturing milestones achieved in the development of the OmniCAR platform.

PTX-100 trial progress
At the end of July, Prescient reported results from the PTX-100 phase 1b basket trial in solid and hematological cancers that demonstrated the drug was very well tolerated at all dose levels.

Early clinical activity was also observed in two patients with aggressive disease, in which prior therapies had failed to stop its progression. One of the patients experienced a partial response (a reduction in cancer burden) from the therapy with no disease progression for 17 months so far, while the other patient experienced a reduction in cancerous lesions and symptomatic .

"In both cases, such patients with refractory T cell lymphoma on standard-of-care therapies would typically be expected to have disease progression within four months, highlighting the encouraging nature of these responses," Prescient reported.

Owing to these encouraging phase 1b results, the company is now progressing development of PTX-100 as a monotherapy in an expansion cohort study in relapsed and refractory T cell lymphoma.

If the expansion cohort is successful, Prescient could advance directly to a separate registration study which may only require small trials compared to typical phase three trials.

Prescient’s other targeted therapy, PTX-200 is currently undergoing a phase 1b clinical trial in patients with acute myeloid leukemia. Updates from this study is expected in coming months.

OmniCAR milestones
To expedite its OmniCAR milestones, Prescient expanded its research partnership with the world-renowned Peter MacCallum Cancer Centre during the June quarter.

The partnership will fast-track development of Prescient’s next generation CAR-T therapy using the OmniCAR platform.

also recently announced "excellent" results from independent in silico immunogenicity testing of OmniCAR’s key binding components, SpyTag and SpyCatcher.

According to the company, this is a key milestone that substantially de-risks the entire platform and is important for progressing Prescient’s in-house programs and external collaborations.

Immunogenicity testing evaluates the immune response against a new therapy. In the case of CAR-T cell therapies, high levels of immunogenicity can adversely impact CAR-T cell expansion and persistence, which can impact the overall safety and clinical response of the treatment.

OmniCAR’s binding system components SpyTag and SpyCatcher were independently tested by a US research provider with results demonstrating that both components have very low immunogenicity – on par with circulating human antibodies.

Prescient chief executive officer and managing director Steven Yatomi-Clarke said the results "could not have been better".

"It gives us confidence that if these therapies are ultimately delivered to patients, their immune systems will not impair the therapy itself."

"This is essential not only for Prescient’s three in-house OmniCAR programs, but also for potential external collaborators, who consider immunogenicity very stringently," he added.

The development followed the successful completion of manufacturing and delivery of critical components of the OmniCAR platform including cell binders for several cancer targets and lentiviral vectors used to produce CAR-T cells.