On March 30, 2022 Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078,) a biotechnology company focused on the discovery and development of innovative peptide-based medicines, reported a corporate restructuring intended to leverage its peptide platform by prioritizing investment in its research and development pipeline programs and streamline its commercial operations (Press release, Zealand Pharmaceuticals, MAR 30, 2022, View Source [SID1234611227]).

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The changes will refocus the Zealand’s resources reducing expenses while investing in strategic development and commercialization partnerships of pipeline assets. Dr Adam Steensberg will replace Emmanuel Dulac as Chief Executive Officer of Zealand as of 30 March 2022.

"The Board is focused on ensuring that the company continues to play to its strengths and believes that Dr. Adam Steensberg, its current Executive Vice President of Research & Development and Chief Medical Officer, has the right skill set and experience having developed the company’s rich and deep pipeline under his tenure," said Martin Nicklasson, Chairman of the Board of Zealand Pharma. "I want to thank Emmanuel for his stewardship of the company over the last three years."

Following a review of all business operations, Zealand plans to maximize the value of V-Go and Zegalogue through strategic partnerships and will restructure its commercial organization in the United States while ensuring continuity of services by maintaining patient, physician, and payor support for V-Go and Zegalogue. Zealand will also seek commercial partnership opportunities for its late-stage clinical pipeline programs as it looks to further leverage its peptide platform though strategic collaborations. With the restructuring, the US workforce will be reduced 90% by Q3 of this year with additional cost reductions implemented in Denmark.

"I realize that these changes impact employees in our organization and we are grateful to all our colleagues for their dedication and all they have done to improve the lives of patients," said Adam Steensberg, President and Chief Executive Officer of Zealand Pharma. "We have made the decision to restructure because we believe that seeking commercial partnerships will generate more value for the company and shareholders as we transform the company into a more focused and cost-effective organization. By improving our operational efficiency and targeting business development efforts, we will be in position to fully leverage the value of our most advanced assets and develop new peptide-based therapies. We have a strong R&D pipeline with Phase III readouts this year for dasiglucagon in CHI and, glepaglutide in SBS in the second and third quarters respectively, and Phase I data for our Amylin analogue targeting obesity later this year."

With the restructuring, the company is updating its financial guidance for 2022.

Net operating expenses in 2022 are now expected to be DKK 1,000 million +/-10%. This is a decrease of DKK 200 million from the prior guidance issued on March 10, 2022, and due to the change in commercial strategy, net product revenue from the sales of commercial products is now expected to be DKK 115 million +/- 10%. This is a decrease of DKK 125 million from the prior guidance and does not include any revenue from existing license agreements or from any potential partnerships. If such partnerships occur, Zealand will update the financial guidance accordingly.

On March 30, 2022 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition") reported that financial results and a business update for the full fiscal year ended December 31, 2021 (Press release, VolitionRX, MAR 30, 2022, View Source [SID1234611226]). Volition management will host a conference call tomorrow, March 31 at 8:00 a.m. U.S. Eastern Time to discuss these results. Conference call details may be found below.

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"I could not be prouder of the team’s achievement in securing a global licensing and supply agreement for our Nu.Q Vet Cancer Screening Test with Heska Corporation, one of the industry’s leading companies," commented Cameron Reynolds, President and Group Chief Executive Officer of Volition. "Volition Veterinary is an exciting, fast-moving part of our business with clear potential to generate significant revenue for the company, initially under our agreements with Heska and SAGE Healthcare, through both milestone payments and ongoing sales of kits and key components. We have also made good progress in other key areas including our Nu.Q NETs and Nu.Q Capture programs as we shift gears towards our goal of becoming a commercial company with products."

An interview with Cameron Reynolds, President and Group Chief Executive Officer of Volition, Dr. Tom Butera, Chief Executive Officer of Volition Veterinary Diagnostics Development LLC, and Terig Hughes, Group Chief Financial Officer of Volition: View Source

Company Highlights

Financial

Cash and cash equivalents as of December 31, 2021, totaled approximately $20.6 million compared with $19.4 million as of December 31, 2020.
Subsequent to year end, Volition is due to receive a $10 million upfront payment as a result of the execution of the agreement with Heska Corporation.
Cash burn rate averaged approximately $2 million per month.
Net loss for the full year of 2021 was $27 million versus $20.4 million for 2020 with this increase primarily due to non-cash items in addition to new hire staffing costs.
Signed our first Nu.Q Discover agreement in 2021 and subsequent to year end have signed an additional five agreements worth an aggregate of approximately $200,000 on a full-year basis.
Made strong progress in improving internal controls and processes and anticipate the remaining weakness regarding segregation of duties in finance will be resolved in 2022.
Commercial Opportunity

We estimate our annual total addressable market ("TAM") to be approximately $70 billion worldwide including Nu.Q Vet, Nu.Q Discover, Nu.Q NETs and Nu.Q Cancer.
All estimates are global and on an annualized basis using key assumptions as follows:
We estimate the Nu.Q Vet TAM to be approximately $11 billion based on global canine and feline populations that are eligible for screening and monitoring and a price assumption of $50 per test to the consumer.
For Nu.Q Discover we estimate the TAM to be over $200 million using drug pipeline data of registered clinical trial programs for relevant epigenetic targets.
We estimate the Nu.Q NETs TAM to be approximately $22 billion calculated using estimated hospital admissions and discharges for sepsis and the associated average length of stay.
We estimate our Nu.Q Cancer TAM to be approximately $37 billion calculated based on eligible populations for annual screening, target participation rates and incidence/prevalence of specific cancers, and risk stratification use cases.
Price per test assumptions for Nu.Q and Nu.Q NETs range from $120 for the U.S., $50 for Europe and $25 for the rest of the world.
Personnel/ Operational

To support our commercial expansion, we welcomed Terig Hughes as our Chief Financial Officer, Gael Forterre as our Chief Commercial Officer, Dr. Tom Butera as the Chief Executive Officer of our veterinary subsidiary, and Mr. Nick Plummer as Group General Counsel.
In addition, Gaetan Michel was promoted to Chief Operating Officer and has relocated to the U.S. to accelerate the development of Volition America.
Dr. Terry Kelly was promoted to Chief Innovation Officer and is building a team focused on cutting-edge, discovery research at our new innovation hub which opened in California in March 2022.
Volition Veterinary

Executed a global licensing and supply agreement with one of the industry’s leading companies, Heska Corporation.
In exchange for granting Heska exclusive worldwide rights to sell the Nu.Q Vet Cancer Screening Test for companion animals at the Point of Care, Volition will receive:
a $10 million upfront payment on signing,
up to $18 million based upon the achievement of near/mid-term milestones, and
ongoing additional revenue for key components.
In addition, Volition has granted Heska non-exclusive rights to sell the Nu.Q Vet Cancer Screening Test in kit format for companion animals, through Heska’s network of central reference laboratories for which Volition will receive ongoing additional revenue for such kit sales.
Appointed SAGE Healthcare as a non-exclusive licensee and distributor of our Nu.Q Vet Cancer Screening Test for the Asian market.
We remain in advanced negotiations with other potential licensing partners in our efforts to make Nu.Q Vet as accessible as possible worldwide and anticipate further announcements in 2022.
Published two peer-reviewed clinical papers and two abstracts at the Veterinary Cancer Society Annual Conference including the first data demonstrating the use of Nu.Q Vet as a disease monitoring tool.
Clinical – NETosis including COVID-19

Volition believes the Nu.Q NETs assay will have wide applicability for monitoring diseases with a NETs component (such as COVID-19, influenza, sepsis, autoimmune diseases, and cancer) and potentially to risk-stratify patients for treatment selection.
Volition expects to register CE marks on its first NETs product, across multiple platforms including ELISA plate, automated beads, and a proof of concept on a very high throughput platform by the summer of 2022.
Volition intends to register the Nu.Q NETs product with a broad almost C-reactive protein (CRP) style claim "for the detection and evaluation of infection, tissue injury, inflammatory disorders and diseases associated with NETosis."
Posters published during 2021 (at the International Society on Thrombosis and Haemostasis Congress) showed that results on admission using the same Nu.Q NETs assay could predict future COVID-19 disease severity and that serial results correlate with disease progression including 28-day mortality.
Further larger studies have been completed in COVID-19 and sepsis which are now awaiting publication, as well as studies in other diseases in progress, with results expected in the coming quarters.
Clinical – Cancer

Published data at ASCO (Free ASCO Whitepaper) GI 2022 for two colorectal cancer studies (asymptomatic and symptomatic populations) conducted with the National Taiwan University.
Results demonstrated that using Nu.Q assays in conjunction with FIT could potentially reduce unnecessary colonoscopies by up to 28% in patients with gastrointestinal symptoms and that this dual approach could also improve the effectiveness of FIT-based screening programs for asymptomatic patients.
The Lung Cancer team at the National Taiwan University has completed collection and preliminary analysis and submitted abstracts to upcoming conferences.
Volition has also undertaken active and continuing negotiations in Asia, in addition to platform development on its first human cancer launch in China.
Collection for the U.S. Early Detection Research Network ("EDRN") study restarted in June 2021 and enrollment has been slow but steady. The EDRN has diverted some efforts to drive recruitment and it still anticipates study completion in the fourth quarter of 2022.
With regards to Volition’s U.S. blood cancer studies, the timing of expected completion for each has been impacted by the COVID-19 pandemic due to sample collection and protocol issues.
Given the pandemic, and resultant delays in the larger Non-Hodgkin Lymphoma ("NHL") study (of 1500 subjects), the Company has taken the opportunity to upgrade the platform to a high-throughput platform which will help facilitate an FDA compliant product. Consequently, Volition now expects this study to initiate recruitment in the second quarter of 2022 with study completion anticipated in 2023.
A smaller, proof of concept NHL monitoring study is ongoing. However, due to missing serial samples as a result of pandemic collection issues, we are not in a position to publish yet. Collection continues and we anticipate analyzing a more complete data set in 2022.
Nu.Q Capture

The Nu.Q Capture program now has several strands of technology which:
essentially remove background noise, thereby amplifying the signal,
look to identify the signal in a novel way including through mass spectrometry, or
isolate various chromatin fragments, including nucleosomes and transcription factors.
Nu.Q Capture, when used in combination with either sequencing, mass spectrometry and/or Volition’s Nu.Q assays could potentially aid diagnosis, treatment selection, and both treatment and disease monitoring in addition to aiding biomarker discovery.
Further to the publication in 2021 of a novel method utilizing Nu.Q Capture and mass spectrometry, Volition is developing a large 1000-plus patient study in lung cancer and colorectal cancer with further announcements expected in 2022.
Intellectual Property

29 patent families (plus three in-licensed families) covering both human and animal use of Volition’s Nucleosomics platform.
84 granted patents (12 in the U.S., 14 in Europe, and 58 rest of world).
93 patents pending worldwide.
Continued focus on filings and expect portfolio to grow in the quarters and years ahead.
Publications

In 2021, data for the Nu.Q platform was presented at five international conferences and Volition has collaborated on four clinical papers.
In 2022, to date, two posters were presented at the ASCO (Free ASCO Whitepaper) GI 2022 conference.
These publications are another very important step forward for the Company.
Upcoming Milestones

Drive near term revenue in the following key areas:
Licensing of its technology, with a particular but not exclusive focus on Nu.Q Vet.
Complete Heska Corporation agreement milestones in order to receive further milestone payments.
Sales of key components of Point of Care test with Heska.
Sales of kits from non-exclusive agreements for the use of Nu.Q Vet via central reference labs.
Ongoing and new Nu.Q Discover agreements.
Sales of its disease monitoring tests (e.g. COVID-19, sepsis).
Continue to progress the research program for the use of Nu.Q in NETosis, in monitoring disease progression of COVID-19, sepsis, and potentially other diseases and as a possible companion diagnostic for a treatment for sepsis.
Continue to advance its previously announced large-scale blood, lung, and colorectal cancer trials in Europe, Asia, and the U.S.
Publish several abstracts and peer-reviewed scientific papers with clinical results showing the robustness and utility of its Nu.Q platform.
Advance the development of Nu.Q Capture.
Continue to file patents to expand and extend its intellectual property portfolio.
VolitionRx Limited Full Fiscal 2021 Financial Results and Business Update

Cameron Reynolds, President and Group Chief Executive Officer of Volition, will host the call along with Terig Hughes, Group Chief Financial Officer of Volition, Dr. Tom Butera, Chief Executive Officer of Volition Veterinary Diagnostics Development LLC, and Scott Powell, Executive Vice President, Investor Relations of Volition.

A live audio webcast of the conference call will also be available on the investor relations page of Volition’s corporate website at View Source

In addition, a telephone replay of the call will be available until April 14, 2022. The replay dial-in numbers are 1-844-512-2921 (toll-free) in the U.S. and Canada and 1-412-317-6671 (toll) internationally. Please use replay pin number 13728406.

On March 30, 2022 LianBio (Nasdaq: LIAN), a biotechnology company dedicated to bringing innovative medicines to patients in China and other major Asian markets, reported financial results for the fourth quarter and year ended December 31, 2021 (Press release, LianBio, MAR 30, 2022, View Source [SID1234611224]).

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"We are proud of our progress over the past year, highlighted by the achievement of key clinical and corporate milestones, including the initiation of the Phase 3 EXPLORER-CN trial of mavacamten in Chinese patients with symptomatic oHCM, and the approval of infigratinib for the treatment of cholangiocarcinoma patients in the Hainan Province in China," said Yizhe Wang, Ph.D., Chief Executive Officer of LianBio. "LianBio continues to advance our pipeline of clinically validated therapeutic candidates and we plan to initiate pivotal studies of three additional programs, TP-03, NBTXR3 and infigratinib, in China by year-end. We remain focused on our cross-border development strategy and are committed to building our pipeline of novel medicines for patients in Greater China and other Asian markets."
Recent Business Highlights and Clinical Development Updates
Phase 3 EXPLORER-CN trial of mavacamten in symptomatic oHCM patients initiated and PK trial dosing completed

•In November 2021, LianBio initiated and completed enrollment and dosing in a pharmacokinetic (PK) study of mavacamten in healthy Chinese volunteers.

•In January 2022, LianBio initiated the Phase 3 EXPLORER-CN clinical trial of mavacamten in Chinese patients with symptomatic oHCM.

•In February 2022, LianBio’s partner Bristol Myers Squibb (BMS) announced positive topline results from the Phase 3 VALOR-HCM trial, evaluating mavacamten in patients with oHCM who are eligible for septal reduction therapy.

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•In February 2022, LianBio announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) granted Breakthrough Therapy Designation in China for mavacamten for the treatment of patients with oHCM.

Infigratinib approved for the treatment of CCA in the Bo’ao pilot zone of Hainan Province
•In December 2021, infigratinib received approval from the Health Commission and Medical Products Administration of Hainan Province, under the special Named Patient Program (NPP), for the treatment of patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement. The approval enables early commercial access to infigratinib in the Bo’ao Lecheng International Medical Tourism Pilot Zone based on the drug’s approval in other global jurisdictions.

Expanded leadership team with key executive hires and named two additions to board of directors
•In October 2021, LianBio named Michael Humphries, MBBS, as Chief Scientific Advisor to guide research and development (R&D) strategy, advance the pipeline, and lead assessment of new in-licensing opportunities.
•In October 2021, LianBio appointed Jesse Wu and Susan Silbermann to the Board of Directors.
Raised $334.5 million of gross proceeds from IPO
•In November 2021, LianBio raised gross proceeds of $334.5 million and aggregate net proceeds of $304.8 million in connection with its initial public offering and subsequent exercise of the underwriters’ option to purchase additional ADSs.

Key Anticipated Milestones Expected in 2022
Mavacamten
BMS-partnered cardiac myosin inhibitor in development for the treatment of hypertrophic cardiomyopathy and certain forms of heart failure
•LianBio’s partner BMS has announced a Prescription Drug User Fee Act (PDUFA) target action date of April 28, 2022 for its New Drug Application to the U.S. Food and Drug Administration (FDA) for mavacamten for the treatment of patients with oHCM.
TP-03
Tarsus Pharmaceuticals-partnered GABA-Cl channel blocker in development for the treatment of Demodex blepharitis (DB) and meibomian gland disease
•LianBio expects to initiate a Phase 3 trial of TP-03 in Chinese patients with DB in the second half of 2022 to support regulatory approval in China.
•LianBio’s partner Tarsus has announced that it expects to report topline data in April 2022 from the ongoing Phase 3 Saturn-2 trial of TP-03 in DB patients.
NBTXR3
Nanobiotix-partnered radioenhancer in development for multiple solid tumor indications
•LianBio expects to begin dosing Chinese patients in Nanobiotix’s ongoing global pivotal Phase 3 trial of NBTXR3 for the treatment of locally advanced head and neck squamous cell carcinoma in elderly patients ineligible for cisplatin in the second half of 2022.

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Infigratinib
QED-partnered FGFR1-3 inhibitor in development for the treatment of individuals with FGFR-driven cancers
•LianBio expects to begin dosing Chinese patients in QED’s ongoing global pivotal Phase 3 PROOF-301 trial of infigratinib in first-line CCA patients with FGFR2 gene fusions/translocations in the second half of 2022.

Fourth Quarter and Full-Year 2021 Financial Results:
Research & Development Expenses

R&D Expenses: Research and development expenses were $7.7 million for the fourth quarter of 2021 compared to $2.7 million for the fourth quarter of 2020, and $158.7 million for the year ended December 31, 2021 compared to $120.9 million for the year ended December 31, 2020. The increase was primarily attributable to increased milestone payments and development activities to support clinical trials and personnel-related expenses (including share-based compensation expense) as a result of increased employee headcount, development activities to support our clinical trials and professional fees.

General & Administrative Expenses

G&A Expenses: General and administrative expenses were $14.4 million for the fourth quarter of 2021 compared to $6.5 million for the fourth quarter of 2020, and $36.9 million for the year ended December 31, 2021 compared to $14.0 million for the year ended December 31, 2020. The increase was primarily attributable to increases in payroll and personnel-related expenses (including share-based compensation expense) for increased employee headcount and increases in legal service costs, consulting costs and accounting services.

Net Loss

Net Loss: Net loss was $21.2 million for the fourth quarter of 2021 compared to net loss of $12.7 million for the fourth quarter of 2020, and $196.3 million for the year ended December 31, 2021 compared to $139.6 million for the year ended December 31, 2020.

Cash Balance

Cash balance: Cash, cash equivalents, marketable securities, and restricted cash at December 31, 2021 totaled $403.2 million, reflecting a net increase of $148.9 million from December 31, 2020. LianBio projects its cash position is sufficient to fund current operations through 2023.

On March 30, 2022 Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company with a Research & Development ("R&D") innovation engine that aims to discover, develop and ultimately deliver impactful medicines to patients, reported financial results for the fourth quarter and year ended December 31, 2021 and provided a business update (Press release, Centessa Pharmaceuticals, MAR 30, 2022, View Source [SID1234611220]).

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"We have strengthened our strategic focus on innovative, high impact rare disease and immuno-oncology assets. Lixivaptan for ADPKD and SerpinPC for hemophilia are entering into registrational studies while LB101, our PD-L1xCD47 LockBody, is advancing toward the clinic," said Saurabh Saha, MD, PhD, Chief Executive Officer. "We are in a strong financial position to make significant clinical progress towards our ‘4×24’ goal of having four programs in registrational trials in 2024."

"We believe that our LockBody programs have the potential to become the cornerstone for a multi-product immuno-oncology franchise. We look forward to sharing initial preclinical data at ASCO (Free ASCO Whitepaper) 2022 for the first program, LB101, which is designed to selectively drive potent CD47 effector function activity while avoiding systemic toxicity," said Antoine Yver, MD, MSc, Chairman of Development.
"The breadth of our rare disease programs provides us multiple opportunities to develop drugs which can potentially impact the lives of thousands of patients living with debilitating diseases such as ADPKD, hemophilia, alpha-1-antitrypsin deficiency, pulmonary arterial hypertension, and narcolepsy, among others," added Javad Shahidi, MD, MSc, Chief Medical Officer.

2021 Highlights and Recent Business Updates

Clinical Development Updates
•SerpinPC: Recently completed pre-IND interactions with the FDA regarding the planned registrational studies for SerpinPC. Based on the FDA feedback, the Company is proceeding with a streamlined, integrated registrational development plan initially for Hemophilia B, with and without inhibitors. The FDA discussions followed the announcement in September 2021 of positive topline data from a proof-of-concept study of SerpinPC in severe Hemophilia A and B subjects not on prophylaxis.
•Lixivaptan: Commenced dosing in the pivotal Phase 3 clinical trial ("ACTION Study") evaluating lixivaptan as a potential treatment for autosomal dominant polycystic kidney disease ("ADPKD"). In addition, a key US patent was issued on February 8, 2022, which covers the use of lixivaptan for the treatment of ADPKD. The patent term expires June 8, 2038, before considering possible patent term extensions or adjustments.
•ZF874: Announced proof-of-mechanism data from the first three PiMZ subjects dosed in the Phase 1 Part B study evaluating ZF874 for the treatment of AATD demonstrating that a pharmacological chaperone has the potential to achieve clinically significant Z-A1AT serum increases in individuals with AATD.
Business Updates
•Further strengthened the leadership team with multiple key appointments, including Antoine Yver, MD, MSc, Executive Vice President and Chairman of Development; Javad Shahidi, MD, MSc, Chief Medical Officer; and David Grainger, PhD, Chief Innovation Officer.
•Dosing of the first subject with lixivaptan in the Phase 3 ACTION Study in February 2022 triggered settlement of the contingent value rights ("CVRs") originally issued to the former shareholders and option holders of Palladio Biosciences in connection with its acquisition by Centessa in January 2021.
•Entered into financing agreement with funds managed by Oberland Capital Management LLC ("Oberland Capital") and received initial $75 million funding in October of 2021.
•As part of ongoing portfolio management, the Company has recently decided to discontinue the small molecule EGFR inhibitor discovery program; evaluate strategic options, including potential divestment, for imgatuzumab; and discontinue internal funding for the lead dual-STAT3/5 degrader program.
•Announced ‘4×24’ portfolio goal with the aim of having four registrational programs in 2024.

Upcoming Program Milestones
Registrational: Programs currently in or expected to enter registrational trials this year:
•Lixivaptan, vasopressin V2 receptor antagonist for ADPKD: Lixivaptan is currently being administered in the Phase 3 registrational ACTION Study to investigate its potential to treat ADPKD and avoid safety issues associated with the only drug currently approved for the treatment of ADPKD. The ACTION Study is expected to enroll ~1,350 subjects across>200 sites in

over 20 countries. The Company anticipates completing enrollment in the second half of 2023 and, if results are supportive, plans to submit a New Drug Application after completion of the one-year double-blind portion of the study.
•SerpinPC, an activated protein C inhibitor for Hemophilia: In the second half of 2022 the Company expects to launch two registrational studies. The first study will enroll ~120 subjects and evaluate the efficacy and safety of prophylactic SerpinPC in subjects with severe Hemophilia B without inhibitors and will include subjects with severe Hemophilia A to add to the safety database. The second registrational study is planned with fewer than 20 subjects to evaluate the efficacy and safety of SerpinPC in subjects with severe Hemophilia B with inhibitors. Registrational plans for Hemophilia A are in development. The Phase 2a open label extension study is ongoing, and we expect to report data on the 48-week flat dose portion of that study and interim results from the following 24-week high dose portion in the fourth quarter of 2022.
Emerging: Programs / platforms with expected clinical proof of concept in the next 18 months
•LB101 and LB201 in Solid Tumors: LB101, a PD-L1xCD47 LockBody, is designed to selectively drive potent CD47 effector function activity while avoiding systemic toxicity. We anticipate sharing foundational preclinical data at ASCO (Free ASCO Whitepaper) 2022, with an IND for LB101 planned for late 2022. LB201, a PD-L1xCD3 LockBody, is designed to selectively drive potent CD3 effector function activity while avoiding systemic toxicity. IND for LB201 is planned for 2023.
•ZF874 in Alpha-1 Antitrypsin Deficiency (AATD): Small molecule folding corrector of the Z variant of alpha-1-antitrypsin. We expect to share Phase 1 data from multiple dose cohorts with PiMZ and PiZZ subjects in 2H 2022.
•MGX292 in Pulmonary Arterial Hypertension (PAH): Recombinant modified BMP9 replacement protein designed to overcome the deficiency in BMP9 signaling in PAH. IND is planned for early 2023.
•OX2R Agonists (Oral and Intranasal) in Narcolepsy Type 1 (NT1): Selective orexin receptor 2 agonists targeting the underlying pathophysiology of orexin neuron loss in NT1. INDs/CTAs are planned for 2023.
Exploratory: Programs with expected clinical proof of concept beyond 18 months
•CBS001 in Inflammatory / Fibrotic Diseases: High-affinity anti-LIGHT antibody. Phase 1 clinical trial in healthy volunteers is expected to begin in the second quarter of 2022.
•CBS004 in Autoimmune Diseases: Humanized mAb targeting BDCA2. IND is planned for late 2022.

Fourth Quarter and 2021 (period January 30 through December 31, 2021) Successor Financial Results
•Cash and Cash Equivalents: $595.1 million as of December 31, 2021 which the Company expects will fund operations, based on current non-risk adjusted plans, into early 2024, without drawing on the remaining available tranches under the Oberland facility.

•R&D Expenses: $41.5 million for the Company for the quarter ended December 31, 2021, $95.7 million for the Successor for 2021.
•General & Administrative Expenses: $13.0 million for the Company for the quarter ended December 31, 2021, $42.9 million for the Successor for 2021.
•Net Loss Attributable to Ordinary Shareholders: $60.8 million for the quarter ended December 31, 2021, $381.1 million for the Successor for 2021 (which includes two special, non-cash expenses: a $220 million charge for acquired in-process R&D associated with the Centessa subsidiary acquisitions; and a $15 million fair value adjustment to the CVRs).

On March 30, 2022 Bolt Biotherapeutics, Inc. (NASDAQ: BOLT) a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported financial results for the fourth quarter and full year ended December 31, 2021, and provided an update on recent business highlights (Press release, Bolt Biotherapeutics, MAR 30, 2022, View Source [SID1234611219]).

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"In 2021, we demonstrated for the first time that our HER2-targeting Boltbody ISAC can increase myeloid cell infiltration and repolarize macrophages in the tumor microenvironment, and thereby, established proof of mechanism for our pioneering Boltbody ISAC platform. In our Phase 1/2 study, BDC-1001 was well tolerated at all dose levels tested with no dose-limiting toxicities. At the lower dose levels evaluated to date, we have seen stable disease in multiple different tumor types and a partial response that has now persisted for more than 60 weeks," said Randall C. Schatzman, Ph.D., Chief Executive Officer of Bolt Biotherapeutics. "We continue to explore dose levels expected to achieve our targeted higher drug exposures, and look forward to determining the recommended Phase 2 dose for BDC-1001 as monotherapy and in combination with Opdivo."

Recent Business Highlights

•Initiation of BDC-1001 combination arm with Bristol Myers Squibb’s PD-1 checkpoint inhibitor OPDIVO (nivolumab) in ongoing Phase 1/2 clinical trial for the treatment of patients with HER2-expressing solid tumors – In December 2021, Bolt Biotherapeutics dosed the first patient in a new combination arm of the ongoing multi-center, multi-dose Phase 1/2 clinical trial of BDC-1001.
•Reported interim Phase 1/2 monotherapy data for BDC-1001 in HER2-expressing solid tumors at ESMO (Free ESMO Whitepaper) I-O 2021 – In December 2021, Bolt Biotherapeutics presented a poster at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2021 detailing new safety, pharmacokinetic, and pharmacodynamic results from 57 subjects, 40 of whom were evaluable for efficacy, in the ongoing monotherapy dose-escalation portion of the Phase 1/2 trial. BDC-1001 demonstrated a favorable safety and tolerability profile. BDC-1001 also demonstrated early signs of clinical activity in the lower doses evaluable for efficacy with corresponding biomarker changes in the tumor microenvironment. The Company expects to determine the recommended Phase 2 dose for expansion trials in 2022.
•Advanced BDC-2034, a Boltbody ISAC targeting CEA, into IND-enabling studies with clinical development expected to begin in 2022 – Bolt Biotherapeutics is conducting IND-enabling studies with the goal of initiating clinical development in 2022. Data presented to date demonstrated tumor cell killing and innate immune activation in cellular and in vivo models of CEA-expressing cancers. Systemic administration in tumor-bearing animals was shown to result in dose-dependent anti-tumor activity.
•Presented preclinical data demonstrating progress of three novel anti-cancer therapeutic candidates at SITC (Free SITC Whitepaper) 2021 – In November 2021, Bolt Biotherapeutics presented three posters highlighting Bolt Biotherapeutics’ pipeline including BDC-2034, a PD-L1 Boltbody ISAC, and BDC-3042, an agonist antibody targeting Dectin-2, a novel target for tumor macrophage reprogramming in cancer immunotherapy.
•Expanded Bolt Biotherapeutics executive leadership team and board of directors with multiple appointments and promotions – The Company added Nicole Onetto, M.D., Brian O’Callaghan, and Frank Lee to the board of directors, bringing deep industry experience in clinical development and commercial strategy within oncology drug development. Jim Healy, M.D., Ph.D., assumed the role of Lead Independent Director. Additionally, Bolt Biotherapeutics promoted Bruce Hug, M.D., Ph.D., to Senior Vice President, Clinical Development & Translational Medicine, Nathan Ihle, Ph.D., to Senior Vice President, Pharmaceutical Operations, and Brian Safina, Ph.D., to Senior Vice President, Discovery Research.
•Cash, cash equivalents, and marketable securities were $271.6 million as of December 31, 2021, which is expected to fund operations and the advancement of the Company’s oncology product pipeline to achieve multiple key milestones into 2024.

Upcoming Events

•At the upcoming 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, the Company will present three posters highlighting preclinical research, demonstrating anti-tumor activity and supporting future clinical development for these novel, early-stage pipeline programs.
oWilliam G. Mallet, Ph.D., will present a poster entitled, "The CEA-targeted ISAC, BDC-2034, shows preclinical efficacy associated with innate immune activation, phagocytosis, and myeloid reprogramming" on Tuesday, April 12, 2022, from 9:00 a.m. – 12:30 p.m. CT.

oShelley E. Ackerman, Ph.D., will present a poster entitled, "Dectin-2 agonist antibodies reprogram tumor-associated macrophages to drive anti-tumor immunity" on Tuesday, April 12, 2022, from 9:00 a.m. – 12:30 p.m. CT.

oJustin Kenkel, Ph.D., will present a poster entitled, "PD-L1-targeted ISAC combines myeloid cell activation, immune-checkpoint inhibition and ADCP to improve anti-tumor efficacy over anti-PD-L1 antibodies in preclinical models" on Wednesday, April 13, 2022, from 9:00 a.m. – 12:30 p.m. CT.

•At the 21st Annual Needham & Co Virtual Healthcare Conference, management will be available for meetings with the investment community on Thursday, April 14, 2022, with a live virtual corporate presentation at 3:45 p.m. ET.

Fourth Quarter and Full Year 2021 Financial Results

Cash Position – Cash, cash equivalents, and marketable securities were $271.6 million as of December 31, 2021, compared to $22.8 million as of December 31, 2020. Bolt Biotherapeutics expects its cash balance to fund operations into 2024.

Collaboration Revenue – Revenue was $0.5 million for the quarter and $1.3 million for the full year ended December 31, 2021, compared to zero and $0.2 million for the same quarter and year in 2020. Revenue in 2021 was generated from services performed under the newly initiated R&D collaboration with Genmab A/S.

Research and Development Expenses – R&D expenses were $22.5 million for the quarter and $75.7 million for the full year ended December 31, 2021, compared to $14.9 million and $40.4 million for the same quarter and year in 2020, primarily due to increase in manufacturing and clinical trial expenses related to BDC-1001 and BDC-2034 and increase in personnel expenses relating to an increase in headcount.

General and Administrative Expenses – G&A expenses were $5.1 million for the quarter and $18.4 million for the full year ended December 31, 2021, compared to $2.1 million and $9.1 million for the same quarter and year in 2020, primarily due to increased expenses related to being a public company, including higher personnel expenses relating to increased headcount and an increase in professional services expenses.

Loss from Operations – Loss from operations was $27.1 million for the quarter and $92.8 million for the full year ended December 31, 2021, compared to $16.9 million and $49.2 million for the same quarter and year in 2020.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform

ISACs are a new category of immunotherapy combining the precision of antibody targeting with the strength of the innate and adaptive immune systems. Boltbody ISACs comprise three primary components: a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant to activate the patient’s innate immune system. By initially targeting a single marker on the surface of a patient’s tumor cells, an ISAC can create a new immune response by activating and recruiting myeloid cells. The activated myeloid cells start a feed-forward loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This reprograms the tumor microenvironment and invokes an adaptive immune response that targets the tumor, which can lead to the conversion of immunologically "cold" tumors to "hot" tumors with the goal of durable responses for patients with cancer.