On February 24, 2022 Genmab A/S (Nasdaq: GMAB) and Seagen Inc. (Nasdaq: SGEN) reported that it will present preliminary data from the innovaTV 207 global, open-label, multicenter phase 2 trial of tisotumab vedotin (TIVDAK) as a monotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN) who experienced disease progression on or after a first-line platinum-containing regimen and a checkpoint inhibitor (Press release, Genmab, FEB 24, 2022, View Source [SID1234608965]). Early results showed tisotumab vedotin demonstrated a manageable safety profile and promising preliminary antitumor activity in this patient population with the primary endpoint of confirmed objective response rate (ORR) per investigator, achieved by 16 percent of patients (95% CI: 5.5 to 33.7). Findings will be presented as part of a plenary session at the American Society for Radiation Oncology (ASTRO) 2022 Multidisciplinary Head and Neck Cancers Symposium on February 25.

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"There is a significant unmet need for additional treatment options for patients diagnosed with squamous cell carcinoma of the head and neck that has progressed despite the use of chemotherapy," said David S. Hong, M.D., deputy chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and lead investigator of the innovaTV 207 clinical trial. "These preliminary data provide important insight into the safety of tisotumab vedotin in this tumor type and demonstrate the value of exploring this potential use further in the innovaTV 207 trial."

The SCCHN cohort of the innovaTV 207 trial enrolled 31 patients with a median age of 65 (range 47 to 78) years whose disease progressed on or after systemic therapy. Patients received 2 milligrams (mg)/kilogram (kg) tisotumab vedotin (maximum dose: 200 mg per infusion) intravenously on day one of each 21-day cycle. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS) per investigator and overall survival (OS). DCR per investigator was 58.1 percent (95% CI: 39.1 to 75.5), median PFS was 4.2 months (95% CI: 2.7 to 4.8), median follow-up was 10.0 months (95% CI: 8.5 to 13.1) and median OS was 9.4 months (95% CI: 8.1 to 11.8). Adverse events were consistent with the known safety profile of tisotumab vedotin: twenty-one (67.7%) patients developed Grade ≥3 treatment-emergent adverse events (TEAEs); most commonly (≥10% of patients) anemia (16.1%), pneumonia (12.9%), and dyspnea (12.9%). Incidence of treatment-emergent serious adverse events (SAEs) was 51.6%, and incidence of treatment-related SAEs was 6.5% (grade 3 hemoptysis [n=1] and grade 3 post-procedural hemorrhage [n=1]).

See TIVDAK U.S. Important Safety Information, including Boxed Warning, below.

"We recognize the high medical need for additional treatment options for patients with head and neck cancers," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "These initial data results are encouraging and underscore the importance of our ongoing clinical trial program that will assess the potential utility of tisotumab vedotin in various cancers."

For more information about the ongoing phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov (Identifier: NCT03485209).

"The presentation of these preliminary data represents another step forward in our work to advance the tisotumab vedotin development program," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "In partnership with Genmab, we will continue to recruit additional patients for trials to further investigate tisotumab vedotin in patients with squamous cell carcinoma of the head and neck, including its potential use as a combination therapy."

About the innovaTV 207 Trial
The phase 2 innovaTV 207 clinical trial evaluates the activity, safety, and tolerability of tisotumab vedotin in selected solid tumors with high tissue factor (TF) expression. The trial is a global, multicenter, open label basket trial which will enroll an estimated 532 adult patients with relapsed, locally-advanced or metastatic disease in separate tumor-specific cohorts. The primary endpoint of the trial is confirmed ORR per investigator, defined as the proportion of patients who achieve a confirmed complete or partial response. Key secondary endpoints include confirmed and unconfirmed ORR, DCR, duration of response, PFS, OS, safety and tolerability. For more information about the phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov (Identifier: NCT03485209).

About Tisotumab Vedotin
Tisotumab vedotin-tftv (TIVDAK) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

In September 2021, the U.S. Food and Drug Administration granted accelerated approval for tisotumab vedotin (TIVDAK) in patients with previously treated recurrent or metastatic cervical cancer. TIVDAK is the first and only approved ADC for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Indication
TIVDAK is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

BOXED WARNING: OCULAR TOXICITY
TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during, and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

Warnings and Precautions
Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8 % of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose. In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

Peripheral Neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barre syndrome. Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients. Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

Monitor patients for pulmonary symptoms of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

Embryo-Fetal Toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

Adverse Reactions
In the innovaTV 204 clinical trial (n=101), serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

Drug interactions

Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

Use in Specific Populations

Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

On February 24, 2022 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported financial results for the fourth quarter and full year ended December 31, 2021 (Press release, Personalis, FEB 24, 2022, View Source [SID1234608981]).

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Fourth Quarter and Recent Highlights

Reported quarterly revenue of $20.7 million in the fourth quarter of 2021 compared with $20.2 million in the fourth quarter of 2020, a 3% increase
Revenue from biopharma and other customers, excluding the VA MVP (as defined below), of $15.4 million in the fourth quarter of 2021 compared with $7.6 million in the fourth quarter of 2020, a 102% increase and a record quarter; revenue from biopharma and other customers includes revenue from Natera at $5.8 million in the fourth quarter of 2021; revenue from biopharma customers excluding Natera at $9.6 million for the fourth quarter of 2021, a 26% increase compared with the fourth quarter of 2020
Revenue from the U.S. Department of Veterans Affairs Million Veterans Program (VA MVP) of $5.3 million in the fourth quarter of 2021 compared with $12.6 million in the fourth quarter of 2020, a decrease of 58%
Launched tumor-informed liquid biopsy assay, NeXT PersonalTM in December 2021; NeXT Personal is designed to deliver industry leading molecular residual disease (MRD) sensitivity down to approximately 1 part-per-million, which is expected to enable earlier detection across a broader set of cancers with low mutational burden and low-shedding cancers
Received first customer order for NeXT Personal in the first quarter of 2022 from a top global pharmaceutical company
Announced a collaboration with the Moores Cancer Center at UC San Diego Health, a National Cancer Institute-designated Comprehensive Cancer Center, to support clinical diagnostic testing in patients with advanced solid tumors and hematological malignancies
Added Olivia Bloom to the Personalis Board of Directors and Audit Committee effective March 1, 2022; Ms. Bloom is a certified public accountant and currently serves as Executive Vice President and Chief Financial Officer of Geron Corporation
Cash, cash equivalents, and short-term investments were $287.1 million as of December 31, 2021
Full Year 2021 Highlights

Reported annual revenue of $85.5 million for the full year of 2021 compared with $78.6 million for the full year of 2020, a 9% increase
Revenue from biopharma and other customers of $39.8 million for the full year of 2021 compared with $22.5 million for the full year of 2020, a 77% increase; revenue from biopharma and other customers includes revenue from Natera of $8.6 million for the full year of 2021; revenue from biopharma customers excluding Natera of $31.2 million for the full year of 2021, a 39% increase
Revenue from the VA MVP of $45.7 million for the full year of 2021 compared with $56.2 million for the full year of 2020, a decrease of 19%; VA MVP unfulfilled orders were approximately $7.6 million at December 31, 2021 and remaining unfulfilled orders are expected to be recognized as revenue from the first quarter through the third quarter of 2022, depending upon sample receipt volume and timing from the VA MVP
"I’m pleased to report that revenue for our oncology business exceeded $15 million in the fourth quarter of 2021 and was nearly $40 million for the full year 2021 and grew 77% over 2020, reflecting consistent execution on our growth initiatives. Customer orders were once again significantly above revenue for both the fourth quarter and full year of 2021. Accordingly, we expect our oncology revenue to grow by more than 50% in 2022 over 2021," said John West, Chief Executive Officer of Personalis. "In addition, we recently received our first customer order for NeXT Personal, our MRD liquid biopsy offering, from a large global pharmaceutical company. We expect NeXT Personal to be an important growth driver for both biopharma and diagnostic test revenue."

Fourth Quarter 2021 Financial Results

Revenue was $20.7 million in the three months ended December 31, 2021
Gross margin was 38.7% in the three months ended December 31, 2021
Operating expenses were $28.2 million in the three months ended December 31, 2021
Net loss was $20.2 million in the three months ended December 31, 2021 and net loss per share was $0.45 based on a weighted-average basic and diluted share count of 44.8 million
Cash, cash equivalents, and short-term investments were $287.1 million as of December 31, 2021
Full Year 2021 Financial Results

Revenue was $85.5 million for the year ended December 31, 2021
Gross margin was 37.0% for the year ended December 31, 2021
Operating expenses were $97.0 million for the year ended December 31, 2021
Net loss was $65.2 million for the year ended December 31, 2021 and net loss per share was $1.49 based on a weighted-average basic and diluted share count of 43.9 million
Full Year 2022 Outlook

Personalis expects the following for the full year of 2022:

Total company revenue is expected to be approximately $67.0 million
Revenue from biopharma and all other customers, excluding the VA MVP, is expected to be approximately $60.0 million, an increase of 51% compared with 2021
Net loss is expected to be in the range of $110.0 million to $115.0 million
Webcast and Conference Call Information

Personalis will host a conference call to discuss the fourth quarter and full year 2021 financial results after market close on Thursday, February 24, 2022 at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time. The conference call can be accessed live over the phone by dialing (866) 220-8061 for U.S. callers or (470) 495-9168 for international callers, using the conference ID: 6877026. The live webinar can be accessed at View Source

On February 24, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing next-generation multifunctional biotherapeutics, reported financial results for the year ended December 31, 2021 and provided a summary of recent business highlights (Press release, Zymeworks, FEB 24, 2022, View Source [SID1234608996]).

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"Since assuming my new role a month ago, I am pleased with our progress to focus on our key strategic priorities and improve our operational performance in order to deliver exceptional results for patients and our investors," said Kenneth Galbraith, Zymeworks’ Chair and Chief Executive Officer. "During 2022 and 2023, we expect to deliver on a number of potential value-driving milestones across the organization through forming new partnerships and collaborations, accelerating enrollment of our two ongoing pivotal trials for zanidatamab, reporting data catalysts for both zanidatamab and ZW49, and showcasing new product candidates developed from our novel platforms."

Business Highlights and Recent Developments

Clinical Program Highlights

"This year will be important for progressing our two clinical-stage product candidates, including the reporting of additional clinical data on both zanidatamab and ZW49," said Neil Klompas, Zymeworks’ Chief Operating Officer. "We look forward to achieving full enrollment for our pivotal trial in BTC by the middle of 2022 and to sharing additional data on our two clinical-stage product candidates at major medical meetings over the course of the next year."

Zanidatamab Advances with Two Pivotal Trials.
HERIZON-GEA-01, a pivotal study evaluating zanidatamab in 1L HER2-positive GEA, continues to enroll patients based on confirmatory data presented in September 2021 at ESMO (Free ESMO Whitepaper) in the 1L GEA setting for zanidatamab in combination with chemotherapy. These data position zanidatamab as a potential new standard of care in the first-line setting, and enrollment for HERIZON-GEA-01 continues with plans to complete by the end of 2023. HERIZON-BTC-01, a pivotal study evaluating zanidatamab in previously-treated advanced HER2-amplified BTC, continues to enroll patients and we expect to complete enrollment by mid-2022.
Multiple data catalysts in 2022 to be presented at major medical meetings, including ASCO (Free ASCO Whitepaper).
Zymeworks, along with our partner BeiGene, has submitted abstracts to be presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting in June. Subject to acceptance of these abstracts, we look forward to sharing important new data from the clinical development program for zanidatamab. In addition, Zymeworks will host a conference call discussing results of these studies after the completion of the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting.
ZW49 Continues to Advance Towards Clinical Data Readout in H2 2022.
Zymeworks’ second clinical-stage asset and first biparatopic HER2-targeting antibody-drug conjugate, ZW49, has completed enrollment of 30 patients in the expansion cohorts targeting 2.5 mg/kg every three weeks. The weekly dosing regimen continues to progress with no dose-limiting toxicities observed to date. We plan to present the results and recommended development path forward at a major medical meeting in the second half of 2022.
Continued Focus on Partnerships and Collaboration

We remain focused on driving value through executing new partnerships and collaborations to support the development of our clinical-stage product candidates, zanidatamab and ZW49, and advancing new antibody-drug conjugate (ADC) or multispecific product candidates based on our novel, next-generation multifunctional therapeutic platforms. We continue to prioritize partnerships and collaborations to fund our operations and further strengthen our financial position.

Throughout 2021 our partnerships continued to advance into the clinical setting, reflected by the receipt of milestone payments in conjunction with Janssen initiating clinical studies with two bispecific antibodies using the Azymetric and EFECT platforms, and BeiGene initiating the pivotal study, HERIZON-GEA-01, in its territory. In tandem, we recognized partnership revenues from the amendment of the Iconic/Exelixis sub-licensing agreement for a ZymeLink ADC. Zymeworks has multiple active collaborations with over $8 billion in potential milestone payments in addition to royalties on potential product sales and has received over $235 million to date.

Corporate Updates

We continue to deliver upon our previously announced cost-efficiency measures and reduction in workforce and expect to exceed our target of reducing employee headcount by at least 25% by March 1, 2022.

With a more focused and efficient workforce, combined with a reduction in operational expenses and the proceeds from our public offering that closed on January 31, we are updating our cash runway guidance into the second half of 2023. Additionally, as we realize additional efficiencies across the organization, and continue to execute on our partnering and monetization initiatives, we expect to be able to extend our cash runway further, and look forward to providing updates in further communications.

In addition, we are pleased to announce that effective immediately, Chris Astle, PhD will be promoted to Senior Vice President and Chief Financial Officer, joining our executive team. Mr. Klompas will continue in the role of Chief Operating Officer.

Chris joined the finance group at Zymeworks in 2021 after relocating from Seattle where he previously served as Vice President at Alder Pharmaceuticals (sold to Lundbeck in 2019 for $1.6 billion). He began his career in the UK, including holding financial positions with Allergan and Gilead. Chris is a Chartered Accountant in the UK and holds a PhD in organic chemistry from the University of Bristol.

"I am thrilled to continue working with Chris in his new position as Senior Vice President and CFO," said Neil Klompas, Chief Operating Officer. "Following the successful hand off of the CFO role, one I have held since 2007, our senior management team will be better positioned to focus on delivering results against the key strategic priorities of our business. We look forward to reporting to our investors on our performance in the weeks and months ahead."

Financial Results for the Year Ended December 31, 2021

Zymeworks’ revenue relates primarily to non-recurring upfront fees, expansion payments or milestone payments from collaboration and license agreements, which can vary in timing and amount from period to period, as well as payments for research and development support. Revenue was $26.7 million in 2021 compared to $39.0 million in 2020. Revenue for 2021 included $8.0 million from BeiGene for a development milestone, $8.0 million from Janssen for two development milestones, $5.0 million from Iconic for partner revenue and $5.7 million from our partners for research and development support under cost sharing arrangements. Revenue for 2020 included $15.0 million from BeiGene for development milestones, $12.0 million from BMS for an expansion fee, $4.0 million from Iconic for partner revenue and $8.0 million from our partners for research and development support under cost sharing arrangements.

We anticipate continuing to receive revenue from our existing and future strategic partnerships, including technology access fees and milestone-based payments. However, our ability to receive these payments is dependent upon either Zymeworks or our collaborators successfully completing specified research and development activities.

Research and development expense was $199.8 million in 2021 compared to $171.2 million in 2020. The increase was primarily due to higher salary and benefit expenses from additional headcount, as well as an increase in zanidatamab clinical trials and other preclinical and research and development expenses which were partially offset by a decrease in drug manufacturing activities. Research and development expenses in 2021 included non-cash stock-based compensation expense of $20.1 million from equity-classified equity awards and a $4.6 million recovery from the non-cash mark-to-market revaluation of certain historical liability-classified equity awards. Excluding stock-based compensation, research and development expenses increased on a non-GAAP basis by $25.4 million for the year ended December 31, 2021 compared to 2020.

We expect research and development expenditures to fluctuate over time in line with the advancement, expansion and completion of the clinical development of our product candidates, as well as our ongoing preclinical research activities.

General and administrative expense was $42.6 million in 2021 compared to $55.2 million in 2020. General and administrative expense included non-cash stock-based compensation expense of $18.2 million from equity-classified equity awards and a $23.8 million recovery from the non-cash mark-to-market revaluation of certain historical liability-classified equity awards. Excluding stock-based compensation expense, general and administrative expense increased on a non-GAAP basis by $9.1 million year over year primarily due to higher salary and benefit expenses from additional headcount, and professional fees, partially offset by a U.S. state sales tax refund recognized in 2021.

In January 2022, we announced that future spending will be focused on our key strategic priorities. In response to this focusing of priorities, we also announced a reduction in workforce of at least 25% to be achieved by the end of 2022. We expect the prioritization and reduction in workforce should result in lower overall spending levels for 2022 and 2023, after accounting for restructuring costs.

Net loss was $211.8 million in 2021 compared to $180.6 million in 2020. The increase in net loss was primarily due to the increases in research and development expenses and decrease in revenue and interest income partially offset by lower general and administrative expense.

As of December 31, 2021, Zymeworks had $252.6 million in cash resources consisting of cash, cash equivalents and short-term investments, which excludes $107.6 million in net proceeds received from our public offering that closed on January 31, 2022. Based on our current operating plan, we believe that our current cash resources, in combination with the anticipated cost savings from the reduction in workforce, proceeds from our public offering, and proceeds from other collaboration payments we anticipate receiving, will enable us to fund our planned operations into the second half of 2023 and potentially beyond.

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 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat cancers and viral diseases, reported that Charles McDermott, President and Chief Executive Officer of Primmune, will present at the 12th Annual Global Life Science Partnering Conference, presented by Biocom California, which will be held Feb. 22 to 24 in San Diego (Press release, Primmune Therapeutics, FEB 24, 2022, View Source [SID1234608982]).

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