On February 24, 2022 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported its financial results for the fourth quarter ended December 31, 2021 and provided an update on the Company’s operations (Press release, BridgeBio, FEB 24, 2022, View Source [SID1234608951]).

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"Focused execution is our top priority in 2022 and we have a busy year ahead, with a strong set of catalysts across our pipeline. While we advance our high-quality programs, we are also taking steps to reduce our operating expenses and will continue to seek additional opportunities to extend our financial runway so that we can deliver meaningful medicines to patients in need as quickly as possible," said Neil Kumar, Ph.D., founder and CEO of BridgeBio.

BridgeBio’s key programs:

Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): The Company’s Phase 3 ATTRibute-CM study did not meet its primary endpoint of change from baseline in six-minute walk distance (6MWD) at Month 12. However, the Company did observe improvements in acoramidis-treated participants versus placebo-treated participants on the Kansas City Cardiomyopathy Questionnaire Overall Score (a quality-of-life measurement), N-terminal pro BNP (a biomarker of heart failure and independent predictor of survival in ATTR-CM), and serum TTR concentration (an in vivo reflection of TTR stabilization). Blinded all-cause mortality events in the ongoing study are consistent with the Company’s expectations given the severity of the enrolled population, the proportion of participants receiving drug and placebo, and the estimated therapeutic benefit of acoramidis. The Company remains confident in the Month 30 primary endpoint, a hierarchical composite including all-cause mortality and cardiovascular hospitalizations. Topline data from the trial are expected in mid-2023.

Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): BridgeBio presented preliminary Phase 2b data for encaleret in an oral presentation at the American Society of Bone and Mineral Research (ASBMR) 2021 Annual Meeting in October. Within five days of individualized dose titration in 13 participants, encaleret normalized mean blood calcium levels and 24-hour urine calcium excretion. Achieving simultaneous blood and urine calcium normalization is a challenge for patients with ADH1 due to the limitations of the current standard of care. If approved, encaleret could be the first therapy on the market for ADH1, a condition caused by gain of function variants in the CASR gene estimated to be carried by 12,000 individuals in the United States alone. BridgeBio plans to share complete data from the Phase 2b study in 2022. The Company also intends to initiate a Phase 3 registrational trial of encaleret in patients with ADH1 in 2022 and anticipates Phase 3 topline data in 2023.

Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia: Initial proof-of-concept data from the ongoing Phase 2 dose-escalation and expansion study is anticipated in mid-2022. Achondroplasia is the most common form of genetic short stature and one of the most common genetic diseases, with a prevalence of over 55,000 cases in the United States and European Union. Low-dose infigratinib is the only known product candidate in clinical development for achondroplasia that is designed to target the disease at its genetic source and the only orally administered product candidate in clinical development.

BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH): Dosed first patient in Phase 1/2 gene therapy trial in January 2022. Initial Phase 1/2 data readout anticipated in second half of 2022. Received Fast Track designation from the U.S. Food and Drug Administration (FDA) in May 2021. CAH is one of the most prevalent genetic diseases potentially addressable with adeno-associated virus (AAV) gene therapy, with more than 75,000 cases estimated in the United States and European Union. The disease is caused by deleterious mutations in the gene encoding an enzyme called 21-hydroxylase, leading to a lack of endogenous cortisol production. BBP-631 is designed to provide a functional copy of the 21-hydroxylase-encoding gene (CYP21A2) and potentially address many aspects of the disease course.

RAS cancer portfolio: BridgeBio announced the discovery of its next-generation KRAS G12C dual inhibitors, the first-known compounds that directly bind and inhibit KRAS in both its active (GTP bound) and inactive (GDP bound) conformations, and PI3ka:RAS breakers, small molecules that block RAS driven PI3Ka activation – a novel approach with the potential to inhibit oncogenic PI3Ka signaling without adverse effects on glucose metabolism. RAS is one of the most well-known oncogenic drivers with approximately 30% of all cancers being driven by RAS mutations, including large proportions of lung, colorectal and pancreatic tumors. BridgeBio expects to select a RAS development candidate in 2022.
Recent pipeline progress and corporate updates:

Debt financing: Secured up to $750 million in non-dilutive debt financing in November 2021. Innovative financing facility and existing cash balance gives BridgeBio access to over $1.2 billion, which is expected to fully fund the Company’s genetic disease and cancer pipeline programs into 2024.

Amgen clinical collaboration: Launched clinical collaboration with Amgen to study BBP-398, a potentially best-in-class SHP2 inhibitor, in combination with LUMAKRAS (sotorasib) in advanced solid tumors with the KRAS G12C mutation. The Phase 1/2 study will include a dose escalation period followed by dose expansion and optimization, and is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of BBP-398 in combination with LUMAKRAS. Under the terms of the non-exclusive collaboration, BridgeBio will sponsor the study and Amgen will provide a global supply of LUMAKRAS.

Helsinn Group strategic collaboration: Established strategic collaboration with the Helsinn Group to co-develop and co-commercialize BridgeBio’s novel GPX4 inhibitor in multiple cancer tumor types. BridgeBio and Helsinn established a non-exclusive framework agreement to identify and potentially co-develop and co-commercialize additional small molecule targeted oncology therapies. The collaboration builds on the $2.45 billion global license and collaboration agreement signed in March 2021 for development of BridgeBio’s FGFR inhibitor infigratinib in oncology indications.

TRUSELTIQ (infigratinib): BridgeBio partner Helsinn Group filed a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) in late 2021 for infigratinib as a second-line or later therapy in patients with advanced and/or metastatic cholangiocarcinoma (CCA) with fibroblast growth factor receptor 2 (FGFR2) fusions or translocations and received EMA acceptance of the MAA in December 2021, confirming that the submission is sufficiently complete to begin the formal review process. In September 2021 Health Canada approved TRUSELTIQ (infigratinib), a small molecule kinase inhibitor that targets FGFR, under the Notice of Compliance with Conditions (NOC/c) policy, for the treatment of adults with previously treated, unresectable locally advanced or metastatic CCA with a FGFR2 fusion or other rearrangement. Australia’s Therapeutic Goods Administration provisionally approved TRUSELTIQ (infigratinib) in November 2021.

BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2i): A Phase 2 trial was initiated in patients with LGMD2i in the first quarter of 2021. If successful, BBP-418 could be the first approved therapy for patients with LGMD2i. With approximately 7,000 patients with potentially treatable mutations, LGMD2i is an inherited recessive muscular dystrophy caused by mutation of fukutin-related protein. A top-line Phase 2 data readout is expected in early 2022. If the readout is successful, BridgeBio anticipates initiating a global Phase 3 clinical trial in the second half of 2022.

BBP-812 – AAV9 gene therapy candidate for Canavan disease: BridgeBio dosed the first patient in its Phase 1/2 trial of BBP-812 for Canavan disease in November 2021. If successful, BridgeBio’s gene therapy could be the first approved therapeutic option for children born with Canavan disease, a devastating and life-threatening condition. An initial Phase 1/2 data readout is expected in the second half of 2022.

BBP-671 – PanK activator for pantothenate kinase-associated neurodegeneration (PKAN) and organic acidemias: BridgeBio has completed the healthy volunteer portion of its Phase 1 trial, demonstrating initial tolerability, target engagement, and suitable PK for BBP-671. BBP-671 has received orphan drug designation as a treatment of propionic acidemia (PA) and PKAN in the United States and the European Union. BBP-671 has also been designated as a drug for a rare pediatric disease for treatment of both PKAN and PA. PKAN Phase 1 data is anticipated in the first half of 2022.

BBP-711 – Glycolate oxidase (GO) inhibitor for hyperoxaluria: Preliminary Phase 1 data showed that BBP-711 was well-tolerated and resulted in maximal increases in plasma glycolate exceeding those achieved by any GO-targeting agents reported in healthy adult volunteers. BBP-711 is being developed for the treatment of primary hyperoxaluria type 1 (PH1) and hyperoxaluria caused by hepatic overproduction of oxalate in recurrent kidney stone formers. A full readout of Phase 1 data in healthy adult volunteers is expected in 2022, to be followed by initiation of a Phase 2/3 trial in PH1 and a Phase 2 proof-of-concept trial in recurrent kidney stone formers.

BBP-589 – Recombinant collagen 7 for recessive dystrophic epidermolysis bullosa (RDEB): BridgeBio completed a Phase 2 clinical trial and anticipates providing data in early 2022. It has initiated a Phase 2 extension study, which will provide BBP-589 to two patients and extend dosing to six months.

BBP-398 – SHP2 inhibitor: BridgeBio is enrolling patients in a Phase 1 monotherapy dose escalation and expansion clinical trial in patients with RAS and RTK mutations. It anticipates providing a clinical update in mid-2022. A Phase 1 monotherapy expansion trial is anticipated to commence in the first half of 2022 to study patients with RTK and NF1 LOF mutations. In 2022, BridgeBio also plans to initiate Phase 1 combination trials with BBP-398 in combination with KRAS G12C, PD-1 and EGFR inhibitors. BridgeBio entered into a co-development agreement with Bristol Myers Squibb in July 2021 for the development of BBP-398 in combination with OPDIVO (nivolumab). BridgeBio launched a clinical collaboration with Amgen in January 2022 to study BBP-398 in combination with LUMAKRAS in advanced solid tumors with the KRAS G12C mutation. A Phase 1 clinical trial studying BBP-398 and osimertinib (EGFR) will be run in China by partner LianBio. LianBio has development and commercialization rights to BBP-398 in mainland China and other select Asian markets.
Fourth Quarter and Full Year 2021 Financial Results:

Cash, Cash Equivalents and Marketable Securities

Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $787.5 million as of December 31, 2021, compared to $607.1 million as of December 31, 2020. Over the past year, the Company repurchased $150.0 million in BridgeBio common stock under its 2021 Share Repurchase Program and $50.0 million in BridgeBio common stock in conjunction with the issuance of its 2029 convertible notes, prepaid in full $124.1 million of term loans, paid $61.3 million for capped call options related to the issuance of its 2029 convertible notes, paid $35.0 million of regulatory-related milestone payments in connection with its FDA-approved products and paid $29.8 million in debt-related interests. Earlier during the year, BridgeBio paid $21.3 million to Eidos Therapeutics, Inc. (Eidos) shareholders who elected for cash settlement in exchange for their Eidos shares and $63.8 million in direct transaction costs arising from the merger with Eidos. These were offset by cash receipts of $731.4 million in net proceeds from the issuance of the 2029 convertible notes, $431.3 million in net proceeds from a loan and security agreement entered into with various lenders, $25.0 million in net proceeds from Hercules Capital, Inc. under an amended loan agreement, and collections of $72.6 million from collaboration partner Helsinn Group. The remaining change in cash, cash equivalents and marketable securities is primarily related to payments of operating costs and expenses.

Cash, cash equivalents and marketable securities, excluding restricted cash, increased by $187.9 million when compared to the balance as of September 30, 2021, which was $599.6 million. During the quarter, the Company received net proceeds of $431.3 million from the loan and security agreement entered into with various lenders and used a portion of the net proceeds to prepay in full the borrowings under the amended loan agreement with Hercules Capital, Inc. for $106.0 million.

Operating Costs and Expenses

Operating costs and expenses for the fourth quarter increased by $50.9 million to $178.5 million in the current quarter as compared to $127.6 million for the same period in the prior year. The increase in operating costs and expenses was due to an increase in personnel and external costs to support the progression of BridgeBio’s research and development programs and staged buildout of its commercial organization as part of commercial launch readiness activities. This increase in personnel and external costs was offset by $12.3 million in reimbursement of expenses from the cost sharing arrangement recognized under BridgeBio’s license and collaboration agreement with Helsinn Group. Stock-based compensation for the quarter was $22.5 million as compared to $12.1 million for the same period in the prior year.

The Company’s research and development expenses have not been significantly impacted by the global COVID-19 pandemic for the period presented. While BridgeBio experienced some delays in certain of its clinical enrollment and trial commencement activities, it continues to adapt in this unprecedented time to enable alternative site, telehealth and home visits, at-home drug delivery, as well as mitigation strategies with its contract manufacturing organizations. The longer-term impact, if any, of COVID-19 on BridgeBio’s operating costs and expenses is currently unknown.

On February 24, 2022 Vaxart, Inc. (NASDAQ: VXRT) reported its business update today for the fourth quarter and full year 2021, reporting forward momentum for the Company, including its oral norovirus and COVID-19 vaccine candidates (Press release, Aviragen Therapeutics, FEB 24, 2022, View Source [SID1234608950]).

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Vaxart said it expected further material progress across its programs in 2022.

"Vaxart made significant progress in 2021 that has us well-positioned to achieve several important milestones in 2022," said Andrei Floroiu, Vaxart’s Chief Executive Officer. "Our potentially transformative oral vaccine programs continued to advance in clinical development. Patient dosing is underway in our U.S. Phase II COVID-19 trial and we have started a Phase II monovalent norovirus GI.1 challenge study."

"We have improved our manufacturing capacity, added to our research and manufacturing ranks, and hired top leadership talent," Floroiu said. "We anticipate building on 2021’s momentum, and are excited about the continued progress we expect to make in 2022, including launching the international clinical studies of our COVID-19 vaccine."

"In 2021, we generated exciting preclinical and clinical data," said Dr. Sean Tucker, Vaxart’s founder and Chief Scientific Officer. "A hamster challenge study showed that our oral COVID-19 vaccine candidate has the potential ability to reduce transmission of SARS-CoV-2, and a Phase I study showed that our vaccine candidate produced broad cross-reactive T cell and IgA responses against both SARS-CoV-2 and other coronaviruses. Therefore, we believe that our COVID-19 vaccine candidate may be reactive against SARS-CoV-2 variants. In 2022, we are planning to conduct additional trials that may highlight the advantages of triggering mucosal immunity as well as of other aspects of our platform."

Recent Business Highlights

Preclinical and Clinical

COVID-19 Vaccine Developments

During the fourth quarter of 2021, Vaxart began Phase II clinical trials of its oral tablet COVID-19 vaccine in the U.S. Vaxart dosed its first subject in late October 2021.

The U.S. portion of the trial is a randomized open-label dose and age escalation lead-in segment in naïve and previously vaccinated subjects. Vaxart expects data from this portion of the trial to be available during the first half of 2022.

In October 2021, a Duke University-led study showed Vaxart’s COVID-19 vaccine candidate reduced the airborne transmission of SARS-CoV-2 virus in an animal model and suggested the vaccine candidate would trigger superior mucosal protection.

The study’s findings, published by bioRxiv, are consistent with those from Vaxart’s Phase II human flu challenge study published in 2020, which showed Vaxart’s oral tablet flu vaccine was better at reducing shedding than the injectable flu vaccine competitor.

In February 2022, Vaxart’s COVID-19 non-human primate study was published by bioRxiv. The study demonstrates that Vaxart’s S-only COVID-19 clinical vaccine candidate, now being studied by Vaxart in Phase II trials, generated antibodies to the original COVID-19 virus strain and to the Beta, Delta, Alpha and Gamma variants of SARS-CoV-2 in the serum and nasal mucosa of non-human primates (NHPs).

Vaxart also announced it would test the cross-reactivity of its oral tablet COVID-19 vaccine candidate against the Omicron SARS-CoV-2 variant in two different studies now expected to begin in March 2022.

In the first study, Vaxart will test the activity of its Phase II COVID-19 oral vaccine candidate against Omicron by analyzing mucosal and serum samples from subjects to whom the vaccine was administered in Vaxart’s current COVID-19 vaccine Phase II trials.

In the second study, Vaxart will conduct an animal Omicron challenge study to assess how its current Phase II COVID-19 vaccine candidate performs in comparison to an Omicron-specific vaccine candidate, which Vaxart is currently developing.

Results from Phase I clinical testing and earlier preclinical testing support Vaxart’s belief that its vaccine candidates may be reactive against Omicron.

Vaxart completed enrollment in its Phase IB placebo-controlled, dose-ranging, repeat dose trial investigating its oral norovirus vaccine candidate in elderly subjects aged 55 to 80 years. This study is designed to evaluate the safety and immunogenicity of Vaxart’s GI.1 vaccine candidate.

The Company expects initial data from this study to be available in the first quarter of 2022 and more complete data to be available by the second quarter of 2022.

Vaxart is conducting an additional GI.1 norovirus vaccine study to evaluate the optimal timing for boost administration under VXA-NVV-105. This study has completed enrollment.

The Company expects initial data from this study to be available in the first quarter of 2022 and more complete data to be available in the first half of 2022.

Vaxart launched a Phase II GI.1 norovirus challenge study in January 2022 to evaluate the safety and clinical efficacy of its oral vaccine candidate. This double blind, placebo-controlled study uses a safe, well-characterized challenge with norovirus GI.1 of volunteers vaccinated with our monovalent norovirus vaccine. The study will yield data on efficacy, safety and immune correlates of protection, with data to be reported in the first quarter of 2023.

Manufacturing Updates

During the fourth quarter of 2021, Vaxart purchased its second clinical manufacturing facility and will be producing vaccines at two plants in parallel. Vaxart expects its manufacturing facilities to produce oral tablet vaccines required for Vaxart’s planned clinical trials in 2022.

Corporate Developments

A new Stanford study published in Cell Host and Microbe found that protection against influenza infection may be achieved through mechanisms other than the development of serum antibodies. The Phase II study demonstrated that VXA-A1.1, an investigational oral tablet flu vaccine under development by Vaxart, had cellular correlates of protection against influenza infection.

Vaxart grew its full-time employee headcount from 28 to 110 during 2021, expanding its research, manufacturing and quality groups as well as its management team to better advance its pipeline of vaccine programs.

In February 2022, Vaxart appointed industry veteran Edward B. Berg as the Company’s first in-house General Counsel. Mr. Berg has practiced law for more than 30 years and has represented Fortune 500 and mid-cap companies in biotechnology, pharmaceuticals and life sciences.

2022 Planned Milestones

Vaxart anticipates the progress and momentum of 2021 will continue into 2022:

Initial data from Vaxart’s Phase II COVID-19 vaccine trials is expected to be available in the first half of 2022.

The Company’s international Phase IB and Phase II COVID-19 trials, including a placebo-controlled efficacy trial in India, are anticipated to begin this year.

Results from two norovirus trials that Vaxart began in 2021 are expected in the first half of 2022.

Financial Results for the Three Months Ended December 31, 2021

Vaxart ended the year with cash, cash equivalents and available-for-sale debt securities of $182.7 million, compared to $204.0 million as of September 30, 2021. The decrease was primarily due to $15.8 million of cash used in operations and $4.8 million spent on a business acquisition.

The Company reported a net loss of $20.8 million for the fourth quarter of 2021, compared to $13.9 million for the fourth quarter of 2020. Net loss per share for the fourth quarter of 2021 was $0.17, compared to a net loss of $0.13 per share in the fourth quarter of 2020. The increase in net loss per share was primarily due to a significant increase in research and development expenses.

Revenue for the fourth quarter of 2021 was $74,000, compared to $356,000 in the fourth quarter of 2020. The decrease was due to lower royalty revenue from sales of Inavir in Japan.

Research and development expenses were $15.5 million for the fourth quarter of 2021, compared to $8.6 million for the fourth quarter of 2020. The increase was mainly due to increases in headcount and related costs and in manufacturing and clinical trial expenses related to our COVID-19 and norovirus vaccine candidates.

General and administrative expenses were $5.8 million for the fourth quarter of 2021, compared to $5.1 million for the fourth quarter of 2020. The increase was mainly due to an increase in headcount and related costs.

Financial Results for the Full Year Ended December 31, 2021

Vaxart reported a net loss of $70.5 million for full year 2021, compared to $32.2 million for full year 2020. Net loss per share for 2021 was $0.58, compared to $0.36 for 2020.

Revenue in 2021 was $892,000, compared to $4.0 million in 2020. The decrease was principally due to lower royalty revenue from sales of Inavir in Japan.

Research and development expenses were $48.7 million for 2021 compared to $19.9 million for 2020. The increase was mainly due to increases in headcount and related costs and in manufacturing and clinical trial expenses related to our COVID-19 and norovirus vaccine candidates.

General and administrative expenses were $21.9 million for 2021 compared to $15.2 million for 2020. The increase was mainly due to increases in personnel costs, D&O insurance and legal and professional fees.

On February 24, 2022 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering the discovery and development of immuno-neurology therapeutics, reported fourth quarter and full year 2021 financial results and summarized recent portfolio and business updates (Press release, Alector, FEB 24, 2022, View Source [SID1234608949]). As of December 31, 2021, Alector’s cash, cash equivalents and investments totaled $735.3 million. In addition, the company received a $200 million payment from partner GlaxoSmithKline (GSK) in January 2022.

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"Over the past year, we made important strides in advancing our clinical and preclinical pipeline of candidates harnessing the innate immune system to address genetically validated targets against neurodegenerative diseases," said Arnon Rosenthal, Ph.D., co-founder and Chief Executive Officer of Alector. "We shared the largest data set to date in individuals with frontotemporal dementia and established a transformative collaboration with GlaxoSmithKline designed to expand and accelerate the development of our progranulin franchise candidates, AL001 and AL101. We are building on this momentum in 2022; with three new INDs on the horizon, we expect to end the year with seven therapeutic candidates in clinical trials. With our strong balance sheet, expanded leadership team, growing development capabilities, maturing pipeline and productive research platform, we are well-positioned to execute our mission."

Recent Clinical Updates and 2022 Milestones

Progranulin Programs: AL001 and AL101

Alector is developing monoclonal antibodies AL001 and AL101 to elevate levels of progranulin in the brain in partnership with GSK. Mutations resulting in progranulin deficiencies are known to be a causal factor for frontotemporal dementia (FTD) and a risk factor for amyloid lateral sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease. In July 2021, Alector entered into a global collaboration with GSK to co-develop and co-commercialize AL001 and AL101. Alector is actively enrolling the INFRONT-3 Phase 3 pivotal clinical study of AL001 in at-risk and symptomatic carriers of frontotemporal dementia with a progranulin mutation (FTD-GRN).

•In January 2022, the journal Trends in Pharmacological Sciences published a review article in press, "Progranulin as a therapeutic target in neurodegenerative diseases" by Alector authors as part of the journal’s special issue, "Advances in neuro-immunology based therapeutic opportunities".

•In November 2021, Alector presented data from the INFRONT-2 Phase 2 open-label clinical study of AL001 in patients with symptomatic FTD-GRN at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) medical meeting.

AL001 restored progranulin to normal levels for the entire duration of treatment. In addition, multiple biomarkers known to be elevated in FTD-GRN decreased toward normal levels following treatment with AL001. Clinical outcome assessments of AL001-treated patients showed slowing of clinical progression by 48% compared to a matched control cohort of participants from the Genetic FTD Initiative (GENFI2).

The totality of the Phase 2 data and consistent response across diverse endpoints support the continued evaluation of AL001 in the ongoing INFRONT-3 Phase 3 study.

AL001 was generally well tolerated when administered monthly for a year or more.

•Twelve-month data from Alector’s INFRONT-2 Phase 2 clinical trial of AL001 in a cohort of patients with FTD with a C9orf72 genetic mutation have been accepted for presentation at the International Conference on Alzheimer’s and Parkinson’s Diseases (ADPD) in March 2022.

•In November 2021 Alector presented interim results from the AL101 first-in-human study of healthy volunteers. The study established that AL101 was effectively distributed into the central nervous system (CNS) and showed proof of mechanism, with increases in progranulin levels observed in the periphery and the brain persisting for one month.
oAL101 was found to be generally well tolerated with single-dose IV or SC administration.
oThe AL101 Phase 1 study is continuing to enroll additional cohorts to test further dosages of AL101 administered intravenously or subcutaneously and is expected to be completed by the end of 2022.

Alzheimer’s Disease Portfolio

AL002 and AL003 are Alector’s clinical-stage immuno-neurology antibodies being advanced for the treatment of Alzheimer’s disease. AL002 is intended to optimize microglial activity in the brain to combat Alzheimer’s disease by binding to the TREM2 receptor to stimulate microglia activity. AL003 blocks the Siglec3, or CD33, checkpoint inhibitor to increase microglia activity. Both are being developed in collaboration with AbbVie.

•In November 2021, Alector presented Phase 1 data for AL003 in healthy volunteers and participants with Alzheimer’s disease at CTAD. AL003 was found to be well tolerated when administered monthly at doses up to and including 15 mg/kg. AL003 demonstrated target engagement of CD33 in both blood and CNS compartments at well tolerated doses.

•In the fourth quarter 2021, Alector reported that Amyloid Related Imaging Abnormalities (ARIA) have been observed in the ongoing AL002 INVOKE-2 Phase 2 clinical trial in Alzheimer’s disease.
oWhile the large majority of ARIA cases observed were asymptomatic and non-serious, a small number of serious adverse events occurred in participants carrying two identical alleles of the

APOE (apolipoprotein E) gene mutation. In addition to protocol amendments voluntarily put in place last year to mitigate risks associated with ARIA, Alector plans to voluntarily amend the Phase 2 trial protocol to exclude APOE e4/e4 homozygotes and to discontinue dosing of APOE e4/e4 homozygotes currently on study. The potential impact, if any, of this protocol amendment on timing to complete enrollment of the INVOKE-2 Phase 2 clinical trial is being assessed.

Early-Stage Pipeline in Neurodegenerative Diseases and Oncology

In 2022 Alector plans to advance three novel therapeutic candidates, including the company’s first immuno-oncology agents, into first-in-human clinical studies.

•A Phase 1 clinical study of treatment with AL008 in patients with advanced solid tumors is expected to begin in the first half of 2022 in China. This first-in-human study will be led by Alector’s regional partner, Innovent Biologics. AL008 is a novel innate immuno-oncology candidate with a dual mechanism of action that combines inhibition of the CD47-SIRP-alpha (SIRPα) pathway with stimulation of activating Fc receptors.

•In November 2021, Alector presented preclinical data from its AL009 immuno-oncology program at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting. In vivo, AL009 led to dose-dependent increases in immune stimulatory molecules consistent with the repolarization of myeloid-derived suppressive cells to a proinflammatory state. A Phase 1 clinical study of AL009 in patients with advanced solid tumors is expected to begin in the second half of 2022. AL009 is a first-in-class multi SIGLEC inhibitor.

•Alector plans to initiate the first-in-human study for AL044 in the second half of 2022. AL044 targets MS4A, a risk gene family for Alzheimer’s disease. MS4A is expressed selectively in microglia and is associated with control of microglia functionality and potential viability.

Recent Corporate News

•In January 2022, Alector received the remaining $200 million from its $700 million committed upfront payment from the GSK collaboration agreement signed by the two companies in July 2021. Under the terms of the agreement, Alector will also be eligible for up to $1.5 billion in potential development, regulatory and commercial milestone payments, as well as profit-sharing in the U.S. and royalties on any ex-U.S. sales.
•Alector expanded its management team with the appointments of Sara Kenkare-Mitra, Ph.D., as Alector’s President and Head of Research and Development, and Marc Grasso, M.D., as Chief Financial Officer.
oDr. Kenkare-Mitra joined Alector in December 2021 from Genentech, where she served as Senior Vice President of Development Sciences. Dr. Kenkare-Mitra brings more than 23 years of experience overseeing the transition of molecules from discovery to the clinic and throughout clinical development.
oDr. Grasso joined Alector from Kura Oncology, where he served as Chief Financial Officer and Chief Business Officer. Prior to Kura, he spent over twenty years in investment banking advising biotechnology and pharmaceutical companies.

Fourth Quarter and Full Year 2021 Financial Results

Revenue. Collaboration revenue for the quarter ended December 31, 2021, was $14.0 million, compared to $4.9 million for the same period in 2020. Collaboration revenue for the year ended December 31, 2021, was $207.1 million compared to $21.1 million for the same period in 2020. The increase in year-over-year collaborative revenue was primarily driven by the strategic collaboration with GSK.

R&D Expenses. Total research and development expenses for the quarter ended December 31, 2021, were $52.8 million compared to $44.4 million for the quarter ended December 31, 2020. Total research and development expenses for the year ended December 31, 2021, were $189.4 million compared to $156.9 million for the same period in 2020. This change in 2021 R&D expenses was mainly driven by increased spending to support advancement of several clinical and preclinical programs, as well as increased personnel-related expenses.

G&A Expenses. Total general and administrative expenses for the quarter ended December 31, 2021, were $16.9 million compared to $13.2 million for the same period in 2020. This increase was primarily due to an increase in personnel-related expenses. Total general and administrative expenses for the year ended December 31, 2021, were $55.0 million compared to $59.4 million for the same period in 2020. This decrease was primarily due to a decrease in legal costs associated with Alector’s arbitration proceedings in 2020 partially offset by an increase in personnel-related expenses.

Net Loss. For the quarter ended December 31, 2021, Alector reported a net loss of $55.6 million, or $0.68 per share, compared to a net loss of $52.2 million, or $0.66 per share, for the same period in 2020. For the year ended December 31, 2021, Alector reported a net loss of $36.3 million, or $0.45 net loss per share, compared to a net loss of $190.2 million, or $2.45 net loss per share, for the same period in 2020.

Cash Position. Cash, cash equivalents, and marketable securities were $735.3 million as of December 31, 2021. In addition, the company received a $200 million payment from partner GSK in January 2022.

Cash Guidance. Alector continues to anticipate that the company’s existing cash, cash equivalents, and marketable securities, including the net proceeds received from GSK in January 2022, are sufficient to fund projected operations into mid-2024.

On February 24, 2022 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism pioneering therapies for genetically defined diseases, reported business highlights and financial results for the fourth quarter and year ended Dec. 31, 2021 (Press release, Agios Pharmaceuticals, FEB 24, 2022, View Source [SID1234608948]).

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"With last week’s FDA approval of PYRUKYND for the treatment of hemolytic anemia in adults with PK deficiency, we have delivered the first therapy for a rare, debilitating, lifelong disease – and we have set the stage for Agios’ next chapter as a leader in the genetically defined disease space," said Jackie Fouse, Ph.D., chief executive officer at Agios. "We have made incredible progress over the past year, following our transformational decision to divest our oncology business and accelerate and expand our genetically defined disease portfolio. We are poised to expand our impact to thalassemia, sickle cell disease, myelodysplastic syndrome and beyond, and I am optimistic about the future we are building together with patient communities, our clinical and research collaborators and our dedicated Agios team."

Fourth Quarter 2021 & Recent Highlights

Received approval from the U.S. Food and Drug Administration (FDA) for PYRUKYND, the first therapy for the treatment of hemolytic anemia in adults with PK deficiency and Agios’ first genetically defined disease medicine.
Dosed first patients in all three pivotal trials of PYRUKYND in thalassemia and sickle cell disease.
Hosted investor day on Nov. 17 to share updates on the company’s research and development pipeline, including progress on the PKM2, BCAT2 and PAH programs, and provide insights into the commercial launch strategy.
Presented the following key data at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition:
Long-term efficacy data of PYRUKYND in adults with PK deficiency who participated in the Phase 3 ACTIVATE and ACTIVATE-T trials
Long-term efficacy and safety data of PYRUKYND in adults with thalassemia who do not receive regular transfusions
Efficacy, safety and translational data of PYRUKYND in sickle cell disease from ongoing collaborator-led studies
Phase 1 healthy volunteer study data of AG-946, the company’s novel PK activator
Anticipated 2022 Key Milestones & Priorities

Agios expects to execute on the following key milestones and priorities in 2022:

Pyruvate Kinase (PK) Deficiency

Receive European Medicines Agency (EMA) regulatory decision for PYRUKYND in adults with PK deficiency by year-end.
Initiate Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies of PYRUKYND in not regularly transfused and regularly transfused pediatric patients with PK deficiency, respectively, in mid-2022.
Thalassemia

Enroll a meaningful portion of patients in the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND in not regularly transfused and regularly transfused adults with thalassemia, respectively, by year-end.
Sickle Cell Disease

Complete enrollment in the Phase 2 portion of the RISE UP study of PYRUKYND in sickle cell disease by year-end.
Initiate the sickle cell disease cohort of the Phase 1 study of novel PK activator AG-946 in the first half of 2022.
Expansion and Acceleration of PK Activation Portfolio

Initiate Phase 2a study of AG-946 in adults with low- to intermediate-risk myelodysplastic syndrome (MDS) by year-end.
Continue to publish clinical and translational data supporting the utility of PK activators across key disease areas and elucidating the burden of disease for PK deficiency, thalassemia and sickle cell disease.
Fourth Quarter and Full Year 2021 Financial Results

The financial results discussion compares Agios’ continuing operations. All periods have been adjusted to exclude discontinued operations related to the divested oncology business.

Research and Development (R&D) Expenses: R&D expenses for continuing operations were $73.3 million for the fourth quarter of 2021 compared to $59.4 million for the fourth quarter of 2020, and $257 million for the year ended Dec. 31, 2021 compared to $220.8 million for the year ended Dec. 31, 2020. This year-over-year increase was largely driven by start-up costs for PYRUKYND pivotal studies, including ENERGIZE, ENERGIZE-T and RISE UP, offset by closeouts of ACTIVATE and ACTIVATE-T studies; regulatory filings for PYRUKYND in the U.S. and EU; and increased workforce spend across R&D.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses for continuing operations were $31.5 million for the fourth quarter of 2021 compared to $25.9 million for the fourth quarter of 2020, and $121.4 million for the year ended Dec. 31, 2021 compared to $115.1 million for the year ended Dec. 31, 2020. This year-over-year increase was driven primarily by PYRUKYND launch preparations and disease education, including field sales build, training and marketing.

Non-Operating Income: Non-operating income included approximately $2.6 million from TIBSOVO (ivosidenib) royalties for the fourth quarter of 2021, and $6.6 million for the year ended Dec. 31, 2021.

Net Loss: Net loss was $98.6 million for the fourth quarter of 2021 compared to a net loss of $84.5 million for the fourth quarter of 2020, and $356.5 million for the year ended Dec. 31, 2021 compared to $329.3 million for the year ended Dec. 31, 2020.

Cash Position and Guidance: Cash, cash equivalents and marketable securities as of Dec. 31, 2021, were $1.3 billion compared to $670.5 million as of Dec. 31, 2020. The company expects that its cash, cash equivalents and marketable securities will enable the company to execute its operating plan through major catalysts and to cash-flow positivity without the need to raise additional equity.

Conference Call Information
Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss fourth quarter and year end 2021 financial results and recent business activities. To participate in the conference call, please dial 1-877-377-7098 (domestic) or 1-631-291-4547 (international) and refer to conference ID 9873227. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

On February 24, 2022 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs) for patients with hematologic malignancies and solid tumors, reported that it will host a conference call and live webcast on Thursday, March 3, 2022 at 8:30 a.m. ET to report financial results for the fourth quarter and year-end 2021 and provide business updates (Press release, ADC Therapeutics, FEB 24, 2022, View Source [SID1234608947]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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To access the live call, please dial 833-303-1198 (domestic) or +1 914-987-7415 (international) and provide conference ID 8189237. A live webcast of the presentation will be available under "Events and Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.