COVID-19 Vaccine (ChAdOx1-S [recombinant])(AstraZeneca Plc)

OXFORD, United Kingdom, Nov. 06, 2024 (GLOBE NEWSWIRE) -- Barinthus Biotherapeutics plc (NASDAQ: BRNS), a clinical-stage biopharmaceutical company developing novel immunotherapeutic candidates that guide T cells to control disease, provided an overview of business updates and announced financial results for the third quarter of 2024. “We continue our strong execution on our clinical trials, completing enrollment in the HBV003 trial of VTP-300 in chronic hepatitis B, and advancing VTP-1000 in celiac disease into the clinic with the first in human study of the novel SNAP-TI platform,” said Dr. Leon Hooftman, Chief Medical Officer of Barinthus Bio. “We expect a data rich fourth quarter from the VTP-300 chronic hepatitis B program, with updated interim readouts from both the HBV003 and IM-PROVE II trials accepted as late-breaking abstracts at the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting® 2024. These updates will provide more mature data than previously disclosed as participants progress and move towards a potential functional cure.” Third Quarter 2024 and Recent Corporate Developments VTP-300 (Chronic hepatitis B) In September 2024, enrollment was completed in the HBV003 trial of VTP-300 in 121 adult participants with chronic hepatitis B. The Phase 2b trial is designed to obtain critical dosing information for a potential functional cure regimen for chronic hepatitis B, with participants receiving VTP-300 and low-dose (LD) nivolumab. Earlier this year, interim data from the HBV003 trial was presented at the European Association for the Study of the Liver (EASL) Congress and demonstrated that treatment with VTP-300 and LD nivolumab was generally well-tolerated and led to a sustained decline in Hepatitis B surface antigen (HBsAg) levels. Seventy-six percent of participants (n=16/21) assessed for nucleos(t)ide analogue (NUC) therapy discontinuation met the criteria. Sixty-seven percent of participants (n=14/21) assessed for NUC discontinuation had HBsAg <10 IU/mL at Week 24 or later. Nineteen percent of the eligible participants (n=4/21) reached undetectable levels of HBsAg, with 2 of these patients maintaining undetectable levels for over 16 weeks. VTP-1000 (Celiac Disease) In September 2024, we initiated the first-in-human Phase 1 AVALON trial of VTP-1000 in adults with celiac disease. The randomized, placebo-controlled clinical trial, which includes a controlled gluten challenge, will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000. VTP-850 (Prostate Cancer) In October 2024, we announced that the PCA001 trial of VTP-850 in men with rising prostate-specific antigen (PSA) after definitive local therapy for prostate cancer (i.e., biochemical recurrence) had completed patient enrollment of 22 participants. The Phase 1 trial is designed to evaluate safety and efficacy, as measured by PSA and T cell response. We expect to have data from the Phase 1 trial in the first half of 2025. Financial Update In October 2024, we were informed that an additional $15.0 million of revenue was due to the Company from Oxford University Innovation (OUI) in relation to the Company's share of royalties received by OUI, as a result of prior commercial sales of Vaxzevria® by AstraZeneca. We expect that this additional cash, when received, will enable us to fund our research and development plans further into the second quarter of 2026. Upcoming Milestones VTP-300 (Chronic hepatitis B) In the fourth quarter of 2024, we expect to announce updated data from the VTP-300 program in ongoing clinical trials in chronic hepatitis B at AASLD – The Liver Meeting® 2024 scheduled from November 15-19, 2024 in San Diego, CA: Updated interim data from HBV003, the Phase 2b trial evaluating additional dosing of VTP-300 and timing of PD-1 inhibition, accepted as a late-breaking oral presentation.Updated interim data from the Phase 2a IM-PROVE II clinical trial evaluating the combination of VTP-300 and Arbutus Biopharma’s imdusiran, accepted as a late-breaking poster. VTP-1000 (Celiac Disease) In the first half of 2025, we expect to announce data from the single ascending dose part of the Phase 1 AVALON trial of VTP-1000 in adults with celiac disease. VTP-850 (Prostate Cancer) In the first half of 2025, we expect to announce results of the Phase 1 PCA001 trial of VTP-850 in men with rising PSA after definitive local therapy for prostate cancer (i.e., biochemical recurrence). Third Quarter 2024 Financial Highlights Cash position: As of September 30, 2024, cash, cash equivalents and restricted cash were $106.1 million, compared to $117.8 million as of June 30, 2024. The net cash used in operating activities was $18.2 million in the third quarter of 2024, primarily resulting from the development of our pipeline and ongoing clinical trials, offset by $6.2 million due to the effect of foreign exchange rates on cash balances. Based on our current operating plans, we expect our available resources to fund operating expenses and capital expenditure requirements into the second quarter of 2026.Revenue: Revenue consisted of $15.0 million in the third quarter of 2024 compared to nil in the second quarter of 2024. Revenue was comprised of the Company’s share of royalties received by OUI as a result of prior commercial sales of Vaxzevria® by AstraZeneca.There is no expectation of additional payments or that we will be notified of such payments in a timely manner.Research and development expenses: Research and development expenses were $11.1 million in the third quarter of 2024 compared to $11.7 million in the second quarter of 2024, with the decrease mainly attributable to a reduction in personnel-related costs as a result of the pipeline prioritization earlier in the year. The quarter-on-quarter R&D expense per program is outlined in the following table. Period ended Three monthsendedSeptember 30,2024 Three monthsended June30, 2024 Change $000 $000 $000 Direct research and development expenses by program: VTP-200 HPV $246 $383 $(137)VTP-300 HBV 2,748 3,034 (286)VTP-500 MERS1 40 304 (264)VTP-600 NSCLC/ESCC2 108 24 84 VTP-850 Prostate cancer 914 414 500 VTP-1000 Celiac 1,751 1,371 380 Other and earlier stage programs 707 908 (201)Total direct research and development expenses $6,514 $6,438 $76 Indirect research and development expenses: Personnel-related (including share-based compensation)3 3,871 4,763 (892)Facility related 214 342 (128)Other indirect costs 540 119 421 Total indirect research and development expenses 4,625 5,224 (599)Total research and development expense $11,139 $11,662 $(523) 1 The development of VTP-500 is funded pursuant to an agreement with the Coalition for Epidemic Preparedness Innovations (CEPI). 2 The VTP-600 NSCLC/Esophageal Squamous-Cell Carcinoma (ESCC) Phase 1/2a trial is sponsored by Cancer Research UK. 3 This includes $0.6 million of personnel-related indirect expenses relating to time spent progressing the VTP-500 MERS program funded by CEPI. General and administrative expenses: General and administrative expenses were $13.4 million in the third quarter of 2024, compared to $7.2 million in the second quarter of 2024. The increase of $6.2 million relates primarily to a loss of $7.7 million on foreign exchange in the third quarter of 2024, compared to a loss of $0.1 million in the second quarter of 2024.Net loss: For the third quarter of 2024, we generated a net loss attributable to shareholders of $8.1 million, or $(0.21) per share on both basic and fully diluted bases, compared to a net loss attributable to shareholders of $16.9 million, or $(0.43) per share on both basic and fully diluted bases in the second quarter of 2024. About Barinthus Bio Barinthus Bio is a clinical-stage biopharmaceutical company developing novel immunotherapeutic candidates designed to guide the immune system to overcome chronic infectious diseases and autoimmunity. Helping people living with serious diseases and their families is the guiding principle at the heart of Barinthus Bio. With a focused pipeline built around our proprietary platform technologies, Barinthus Bio is advancing immunotherapeutic product candidates in infectious diseases and autoimmunity, including: VTP-300, that utilizing our ChAdOx/MVA platform designed as a potential component of a functional cure for chronic HBV infection and VTP-1000, utilizing our SNAP-Tolerance Immunotherapy (SNAP-TI) platform and is designed to treat people with celiac disease. Barinthus Bio is also conducting a Phase 1 clinical trial for VTP-850, a second-generation immunotherapeutic candidate designed to treat recurrent prostate cancer. Barinthus Bio’s differentiated technology platforms and therapeutic approach, coupled with deep scientific expertise and focus on clinical development, uniquely positions the company to navigate towards delivering treatments that improve the lives of people with chronic infectious diseases and autoimmunity. For more information, visit www.barinthusbio.com. Barinthus Bio intends to use the Investors section of its website, its X (formerly known as Twitter) account at @Barinthusbio and its LinkedIn account at linkedin.com/company/barinthus-bio as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor Barinthus Bio’s website, its X account and its LinkedIn account in addition to following Barinthus Bio’s press releases, SEC filings, public conference calls, presentations, and webcasts. Forward Looking Statements This press release contains forward-looking statements regarding Barinthus Bio within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, which can generally be identified as such by use of the words “may,” “will,” “plan,” “forward,” “encouraging,” “believe,” “potential,” “expect,” and similar expressions, although not all forward-looking statements contain these identifying words. These forward-looking statements include, without limitation, express or implied statements regarding our future expectations, plans and prospects, including our product development activities and clinical trials, including timing for readouts of any preliminary, interim or final data for any of our programs, our anticipated regulatory filings and approvals, our cash runway, the potential benefits of our product candidates, and our ability to develop and advance our current and future product candidates and programs. Any forward-looking statements in this press release are based on our management’s current expectations and beliefs and are subject to numerous risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to the success, cost and timing of our pipeline development activities and planned and ongoing clinical trials, including the risk that the timing for preliminary, interim or final data or initiation of our clinical trials may be delayed, the risk that interim or topline data may not reflect final data or results, our ability to execute on our strategy, regulatory developments, the risk that we may not achieve the anticipated benefits of our pipeline prioritization and corporate restructuring, our ability to fund our operations and access capital, our cash runway, including the risk that our estimate of our cash runway may be incorrect, global economic uncertainty, including disruptions in the banking industry, the conflicts in Ukraine, Israel and Gaza, and other risks identified in our filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We expressly disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. BARINTHUS BIOTHERAPEUTICS PLC CONSOLIDATED BALANCE SHEETS (IN THOUSANDS, EXCEPT NUMBER OF SHARES AND PER SHARE AMOUNTS) (UNAUDITED) September 30,2024 December 31,2023ASSETS Cash, cash equivalents and restricted cash$106,102 $142,090 Contract asset - related parties 14,969 — Research and development incentives receivable 5,403 4,908 Prepaid expenses and other current assets 8,180 9,907 Total current assets 134,654 156,905 Goodwill 12,209 12,209 Property and equipment, net 10,719 11,821 Intangible assets, net 22,737 25,108 Right of use assets, net 7,444 7,581 Other assets 926 882 Total assets$188,689 $214,506 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable 3,076 1,601 Accrued expenses and other current liabilities 7,966 9,212 Deferred income 2,044 — Operating lease liability - current 1,986 1,785 Total current liabilities 15,072 12,598 Non-current liabilities: Operating lease liability - non-current 10,683 11,191 Contingent consideration 1,610 1,823 Other non-current liabilities 1,406 1,325 Deferred tax liability, net 457 574 Total liabilities$29,228 $27,511 Commitments and contingencies (Note 15) Stockholders’ equity: Ordinary shares, £0.000025 nominal value; 39,542,518 shares authorized, issued and outstanding (December 31, 2023: authorized, issued and outstanding: 38,643,540) 1 1 Deferred A shares, £1 nominal value; 63,443 shares authorized, issued and outstanding (December 31, 2023: authorized, issued and outstanding: 63,443) 86 86 Additional paid-in capital 391,882 386,602 Accumulated deficit (217,124) (176,590)Accumulated other comprehensive loss – foreign currency translation adjustments (15,551) (23,315)Total stockholders’ equity attributable to Barinthus Biotherapeutics plc shareholders 159,294 186,784 Noncontrolling interest 167 211 Total stockholders’ equity$159,461 $186,995 Total liabilities and stockholders’ equity$188,689 $214,506 BARINTHUS BIOTHERAPEUTICS PLC CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (IN THOUSANDS, EXCEPT NUMBER OF SHARES AND PER SHARE AMOUNTS) (UNAUDITED) Three months ended Nine months ended September 30,2024 September 30,2023 September 30,2024 September 30,2023License revenue 1$14,969 $— $14,969 $802 Total revenue 14,969 — 14,969 802 Operating expenses Research and development 11,139 15,144 33,926 38,501 General and administrative 13,420 961 26,615 26,227 Total operating expenses 24,559 16,105 60,541 64,728 Other operating income 210 — 992 — Loss from operations (9,380) (16,105) (44,580) (63,926)Other income/(expense): Interest income 631 196 2,041 2,306 Interest expense (17) (7) (41) (21)Research and development incentives 608 1,205 1,895 2,921 Other income/(expense) 26 (2) 46 308 Total other income, net 1,248 1,392 3,941 5,514 Loss before income tax (8,132) (14,713) (40,639) (58,412)Tax benefit 3 603 47 2,255 Net loss (8,129) (14,110) (40,592) (56,157)Net loss attributable to noncontrolling interest 15 38 58 103 Net loss attributable to Barinthus Biotherapeutics plc shareholders (8,114) (14,072) (40,534) (56,054) Weighted-average ordinary shares outstanding, basic 39,419,447 38,533,833 39,079,259 38,320,208 Weighted-average ordinary shares outstanding, diluted 39,419,447 38,533,833 39,079,259 38,320,208 Net loss per share attributable to ordinary shareholders, basic$(0.21) $(0.37) $(1.04) $(1.46)Net loss per share attributable to ordinary shareholders, diluted$(0.21) $(0.37) $(1.04) $(1.46) Net loss$(8,129) $(14,110) $(40,592) $(56,157)Other comprehensive gain/(loss) – foreign currency translation adjustments 9,191 (7,820) 7,778 2,364 Comprehensive income/(loss) 1,062 (21,930) (32,814) (53,793)Comprehensive loss attributable to noncontrolling interest 5 48 44 100 Comprehensive income/(loss) attributable to Barinthus Biotherapeutics plc shareholders$1,067 $(21,882) $(32,770) $(53,693) 1 Includes license revenue from related parties for the three and nine months ended September 30, 2024 of $15.0 million (three and nine months ended September 30, 2023: nil and $0.8 million, respectively). IR contacts:Christopher M. Calabrese Managing Director LifeSci Advisors+1 917-680-5608ccalabrese@lifesciadvisors.com Kevin GardnerManaging DirectorLifeSci Advisors+1 617-283-2856kgardner@lifesciadvisors.com Media contact:Audra FriisSam Brown, Inc.+1 917-519-9577audrafriis@sambrown.com Company contact:Jonothan BlackbournIR & PR ManagerBarinthus Bioir@barinthusbio.com

With regards to the AstraZeneca and Johnson & Johnson vaccines, the findings concretely implicate the adenovirus as the culprit behind rare cases of vaccine-induced immune thrombocytopenia and thrombosis. The rare, deadly blood clots triggered by an autoimmune response to the COVID-19 vaccines from Johnson & Johnson and AstraZeneca seem to be caused by a gene that’s also responsible for an unusual but almost identical reaction to the virus that causes the common cold. The findings could have implications for future vaccines.  In a letter published May 15 in The New England Journal of Medicine, an international team of scientists explained that people who carry certain variants of a gene called IGLV3-21*02 are predisposed to developing both vaccine-induced immune thrombocytopenia and thrombosis (VITT) and the same type of reaction after infection with the adenovirus. Both the J&J and AstraZeneca vaccines are delivered to the body in adenovirus vectors, which explains why the etiology of the conditions is the same.  “Our findings have the important clinical implication that lessons learned from VITT are applicable to rare cases of blood clotting after adenovirus infections, as well as having implications for vaccine development," Tom Gordon, M.D., Ph.D., of Flinders University, who led the co-study, said in a press release. Theodore Warkentin, M.D. from McMaster University in Canada and Andreas Greinacher, M.D., from Greifswald University in Germany also led the work.  AstraZeneca’s vaccine, Vaxzevria, was dogged by reports of VITT not long after the shot rolled out in Europe. Soon after, news of VITT in six U.S. patients who took the J&J vaccine emerged as well, prompting officials to pause it to investigate and later restrict its use. It was removed from the market entirely two years later. AstraZeneca’s shot remained available in some parts of Europe until May 2024, when the company requested its marketing approval be revoked due to a decline in demand.  As of May 2023, the same month J&J’s vaccine was pulled, there had been 60 cases of VITT reported in the U.S., including nine deaths. The last count for VITT cases related to AstraZeneca’s vaccine in the U.K. before it was taken off the market was 455, with 81 deaths, according to the U.K.'s healthcare watchdog the Medicines and Healthcare products Regulatory Agency.  The reactions are caused by antibodies against the protein platelet factor 4, or PF4, a protein involved in blood clotting. In 2022, Gordon and his colleagues used a screening method called antibody proteomics to show that antibodies expressed by a variant of IGLV3-21*02 targeted PF4. Genetic analysis of five patients who developed VITT after getting the AstraZeneca vaccine showed that all of them had this gene variant.  Then, in 2023, another research team reported that adenovirus infection led to the same anti-PF4 antibodies and immune thrombocytopenia and thrombosis. The pathogenesis was identical to VITT; this was the first signal of an “anti-PF4 disorder,” as the researchers called it, that might share its etiology.  The two groups teamed up to validate their hypotheses. When they analyzed the structure of the anti-PF4 antibodies from patients in each group and superimposed them, they found they were “extremely similar,” as they wrote in the NEJM letter.  “Such an extraordinary level of autoantibody fingerprint identity between two disorders—at the level of patient-derived antibodies—strongly indicates that VITT and the anti-PF4 disorder that is associated with adenoviral infection are a distinct class of adverse immune responses associated with viral (presumably, adenoviral) structures,” the researchers wrote.  With regards to the AstraZeneca and J&J vaccines, the findings concretely implicate the adenovirus as the cause of VITT rather than other ingredients. But while the researchers know that the immune response to the virus triggers the creation of antibodies to PF4, they still need to identify the antigen, or the proteins or sugars on the virus, that stimulates their creation. This would potentially enable them to genetically engineer the adenovirus vector so it doesn’t have the antigen and, thus, makes adenovirus-based vaccines safer. The team behind the new NEJM paper is currently investigating the antigenic epitope, or the part of the antigen the immune system recognizes, Gordon confirmed to Fierce Biotech Research in an email.  Previously, the Flinders scientists said it may be possible to create a genetic test that can identify patients at risk of VITT as well as to come up with a therapy that neutralizes the anti-PF4 antibodies.  In a statement to Bloomberg earlier this week, an AstraZeneca spokesperson said the company “welcomes any further examination of the possible underlying mechanism of thrombosis with thrombocytopenia syndrome.” J&J told the outlet in an email that it supports the research as well and that “more data are needed to fully understand potential factors that may be associated with this rare event.”