A clinical trial to determine the safety, tolerability and immunogenicity of the candidate Mycobacterium avium subspecies paratuberculosis (MAP) vaccines ChAdOx2 HAV and MVA HAV in patients with active Crohn’s disease

Start Date04 May 2021

Sponsor / Collaborator

HAV Vaccines Limited

NCT04607850 / CompletedPhase 1/2

A Phase 1b/2, Randomised, Placebo-controlled, Dose-ranging Study to Evaluate Safety, Tolerability and Immunogenicity of a Chimpanzee Adenovirus (ChAdOx1)-Vectored Multigenotype High Risk Human Papillomavirus (hrHPV) Vaccine and Modified Vaccinia Ankara (MVA)-Vectored Multigenotype hrHPV Vaccine in Women With Low-grade HPV-related Cervical Lesions

A Phase 1b/2 multi-centre study evaluating the safety, efficacy and immunogenicity of prime-boost vaccines ChAdOx1-HPV and MVA-HPV in women with HPV related low grade cervical lesions.

Start Date16 Mar 2021

Sponsor / Collaborator

Vaccitech (UK) Ltd.

100 Clinical Results associated with VTP-200

100 Translational Medicine associated with VTP-200

100 Patents (Medical) associated with VTP-200

Literatures (Medical) associated with VTP-200

01 Oct 2024·Journal for ImmunoTherapy of Cancer

Novel H-2D^b-restricted CD8 epitope derived from mouse MAGE-type antigen P1A mediates antitumor immunity in C57BL/6 mice

Article

Author: Van den Eynde, Benoit J ; Vigneron, Nathalie ; Ahmad, Maryam ; Stroobant, Vincent ; Noblecourt, Laurine ; Steffke, Emily ; Chandrasekar, Vineethkrishna ; Ramirez-Valdez, Ramiro Andrei ; Lesenfants, Julie ; Wicki, Amanda ; McAuliffe, James ; Hu, Yushu ; Guo, Shi Yu William ; Pereira-Almeida, Vinnycius ; Leung, Carol Sze Ki ; Panetti, Silvia

Background:

Melanoma antigen gene (MAGE)-type antigens are promising targets for cancer immunotherapy as they are expressed in cancer cells but not in normal tissues, except for male germline cells. The mouse P1A antigen shares this MAGE-type expression pattern and has been used as a target antigen in preclinical tumor models aiming to induce antitumor CD8+T-cell responses. However, so far only one MHC I-restricted P1A epitope has been identified. It is presented by H-2Ldin mice of the H-2dgenetic background such as DBA/2 and BALB/c. Given the availability of multiple genetically altered strains of mice in the C57BL/6 background, it would be useful to define P1A T-cell epitopes presented by the H-2bhaplotype, to facilitate more refined mechanistic studies.

Methods:

We employed a heterologous prime-boost vaccination strategy based on a chimpanzee adenovirus (ChAdOx1) and a modified vaccinia Ankara (MVA) encoding P1A, to induce P1A-specific T-cell responses in C57BL/6 mice. Vaccine-induced responses were measured by intracellular cytokine staining and multiparameter flow cytometry. We mapped the immunogenic CD8 epitope and cloned the cognate T-cell receptor (TCR), which we used for adoptive cell therapy.

Results:

ChAdOx1/MVA-P1A vaccination induces a strong P1A-specific CD8+T-cell response in C57BL/6 mice. This response is directed against a single 9-amino acid peptide with sequence FAVVTTSFL, corresponding to P1A amino acids 43–51. It is presented by H-2Db. P1A vaccination, especially with ChAdOx1 administered intramuscularly and MVA delivered intravenously, protected mice against P1A-expressing EL4 (EL4.P1A) tumor cell challenge. We identified and cloned four TCRs that are specific for the H-2Db-restricted P1A43-51peptide. T cells transduced with these TCRs recognized EL4.P1A but not MC38.P1A and B16F10.P1A tumor cells, likely due to differences in the proteasome subtypes present in these cells. Adoptive transfer of these T cells in mice bearing EL4.P1A tumors reduced tumor growth and increased survival.

Conclusions:

We identified the first CD8+T-cell epitope of the MAGE-type P1A tumor antigen presented in the H-2bbackground. This opens new perspectives for mechanistic studies dissecting MAGE-type specific antitumor immunity, making use of the wealth of genetically altered mouse strains available in the C57BL/6 background. This should facilitate the advancement of specific cancer immunotherapies.

01 Jul 2024·Lancet Microbe

Assessment of CD8+ T-cell mediated immunity in an influenza A(H3N2) human challenge model in Belgium: a single centre, randomised, double-blind phase 2 study

Article

Author: Van Leuven, Katrin ; Castellino, Flora ; Kowalik Dobczyk, Monika ; Asher, Jason ; Rutkowski, Kathryn ; Walley, Ana Marie ; Thacker, Juilee ; Klein, Jelle ; Laurent, Cyril ; van Baalen, Carel ; Tucker, Gwen ; Filkov, Ella ; Eagling-Vose, Elizabeth ; Donabedian, Armen ; Ellis, Chris ; Evans, Thomas G ; Treanor, John

BACKGROUND:

Protection afforded by inactivated influenza vaccines can theoretically be improved by inducing T-cell responses to conserved internal influenza A antigens. We assessed whether, in an influenza controlled human infection challenge, susceptible individuals receiving a vaccine boosting T-cell responses would exhibit lower viral load and decreased symptoms compared with placebo recipients.

METHODS:

In this single centre, randomised, double-blind phase 2 study, healthy adult (aged 18-55 years) volunteers with microneutralisation titres of less than 20 to the influenza A(H3N2) challenge strain were enrolled at an SGS quarantine facility in Antwerp, Belgium. Participants were randomly assigned double-blind using a permuted-block list with a 3:2 allocation ratio to receive 0·5 mL intramuscular injections of modified vaccinia Ankara (MVA) expressing H3N2 nucleoprotein (NP) and matrix protein 1 (M1) at 1·5 × 10⁸ plaque forming units (4·3 × 10⁸ 50% tissue culture infectious dose [TCID₅₀]; MVA-NP+M1 group) or saline placebo (placebo group). At least 6 weeks later, participants were challenged intranasally with 0·5 mL of a 1 × 10⁶ TCID₅₀/mL dose of influenza A/Belgium/4217/2015 (H3N2). Nasal swabs were collected twice daily from day 2 until day 11 for viral PCR, and symptoms of influenza were recorded from day 2 until day 11. The primary outcome was to determine the efficacy of MVA-NP+M1 vaccine to reduce the degree of nasopharyngeal viral shedding as measured by the cumulative viral area under the curve using a log-transformed quantitative PCR. This study is registered with ClinicalTrials.gov, NCT03883113.

FINDINGS:

Between May 2 and Oct 24, 2019, 145 volunteers were enrolled and randomly assigned to the MVA-NP+M1 group (n=87) or the placebo group (n=58). Of these, 118 volunteers entered the challenge period (71 in the MVA-NP+M1 group and 47 in the placebo group) and 117 participants completed the study (71 in the MVA-NP+M1 group and 46 in the placebo group). 78 (54%) of the 145 volunteers were female and 67 (46%) were male. The primary outcome, overall viral load as determined by quantitative PCR, did not show a statistically significant difference between the MVA-NP+M1 (mean 649·7 [95% CI 552·7-746·7) and placebo groups (mean 726·1 [604·0-848·2]; p=0·17). All reported treatment emergent adverse events (TEAEs; 11 in the vaccination phase and 51 in the challenge phase) were grade 1 and 2, except for two grade 3 TEAEs in the placebo group in the challenge phase. A grade 4 second trimester fetal death, considered possibly related to the MVA-NP+M1 vaccination, and an acute psychosis reported in a placebo participant during the challenge phase were reported.

INTERPRETATION:

The use of an MVA vaccine to expand CD4⁺ or CD8⁺ T cells to conserved influenza A antigens in peripheral blood did not affect nasopharyngeal viral load in an influenza H3N2 challenge model in seronegative, healthy adults.

FUNDING:

Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority; and Barinthus Biotherapeutics.

01 Jul 2024·VACCINE

Serologic responses to the MVA-based JYNNEOS mpox vaccine in a cohort of participants from the District of Columbia (D.C.)

Article

Author: Carson, William C ; Griffin, Isabel ; Navarra, Terese ; Satheshkumar, Panayampalli S ; Mangla, Anil ; Willut, Christina ; Hutson, Christina L ; Lujan, Leah ; Berry, Isha ; Townsend, Michael B ; Priyamvada, Lalita ; Still, Will ; Lee, Michelle ; Noiman, Adi ; Jackson, David A ; Shelus, Victoria ; Waltenburg, Michelle A ; Beverley, Jason

We assessed early antibody responses after two doses of JYNNEOS (IMVANEX) mpox vaccine in the District of Columbia (D.C.) in persons at high risk for mpox without characteristic lesions or rash. Participants with PCR mpox negative specimens (oral swab, blood, and/or rectal swab) on the day of receipt of the first vaccine dose and who provided a baseline (day 0) serum sample and at least one serum sample at ∼28, ∼42-56 days, or 180 days post vaccination were included in this analysis. Orthopoxvirus (OPXV)-specific IgG and IgM ELISAs and neutralizing antibody titers were performed, and longitudinal serologic responses were examined. Based on participants' IgG and IgM antibody levels at baseline, they were categorized as naïve or non-naïve. Linear mixed effects regression models were conducted to determine if IgG antibody response over time varied by age, sex, HIV status, and route of administration for both naïve and non-naïve participants. Among both naïve and non-naïve participants IgG seropositivity rates increased until day 42-56, with 89.4 % of naïve and 92.1 % of non-naïve participants having detectable IgG antibodies. The proportion of naive participants with detectable IgG antibodies declined by day 180 (67.7 %) but remained high among non-naïve participants (94.4 %). Neutralizing antibody titers displayed a similar pattern, increasing initially post vaccination but declining by day 180 among naïve participants. There were no significant serologic response differences by age, sex, or HIV status. Serologic response did vary by route of vaccine administration, with those receiving a combination of intradermal and subcutaneous doses displaying significantly higher IgG values than those receiving both doses intradermally. These analyses provide initial insights into the immunogenicity of a two-dose JYNNEOS PEP regimen in individuals at high risk of mpox exposure in the United States.

News (Medical) associated with VTP-200

06 Nov 2024

·www.globenewswire.com

Barinthus Bio Reports Third Quarter 2024 Update on Corporate Developments and Financial Results

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

Phase 2Clinical ResultPhase 1Financial Statement

08 Aug 2024

·www.globenewswire.com

Barinthus Bio Reports Second Quarter 2024 Update on Corporate Developments and Financial Results

OXFORD, United Kingdom, Aug. 08, 2024 (GLOBE NEWSWIRE) -- Barinthus Biotherapeutics plc (NASDAQ: BRNS), a clinical-stage biopharmaceutical company developing novel T cell immunotherapeutic candidates, provided an overview of the Company’s progress and announced its financial results for the second quarter of 2024. “Following the positive VTP-300 Phase 2 data in hepatitis B virus (HBV) in the second quarter, we made the strategic decision to prioritize our HBV and celiac disease programs. These two programs have the greatest probability for success and value creation, and represent significant opportunities in therapeutic areas with substantial unmet patient need,” said Bill Enright, Chief Executive Officer of Barinthus Bio. "We are very excited as we plan to initiate our first in human clinical trial of VTP-1000 in celiac disease in the third quarter, utilizing our novel SNAP-TI platform. Celiac disease is an increasingly common autoimmune disease with no FDA or EMA-approved treatments. Towards the end of the year we look forward to sharing updated data from our HBV program as our two Phase 2 trials utilizing VTP-300, which are evaluating a potential functional cure regimen, mature further." Second Quarter 2024 and Recent Corporate Developments Clinical developments: VTP-300 (HBV) In June 2024, we announced updated data from two ongoing Phase 2 clinical trials in people with chronic hepatitis B (CHB) at the European Association for the Study of the Liver (EASL) Congress 2024. The presentations included updated interim data from the Phase 2b clinical trial (HBV003), as well as updated interim data from the Phase 2a clinical trial (IM-PROVE II, AB-729-202) in partnership with Arbutus Biopharma, both in people with CHB receiving ongoing standard of care nucleos(t)ide analogue (NUC) therapy. Interim HBV003 data: VTP-300 and Low-dose Nivolumab Interim data from the HBV003 trial showed; Nearly 20% of participants across the groups had undetectable HBsAg and this was maintained for ≥16 weeks in the two cases who had reached that time point. 76% of participants were eligible for NUC discontinuation.71% of those who did discontinue remained off NUCs at time of data cutoff on April 15, 2024.67% of participants across all groups assessed for NUC discontinuation had HBsAg <10 IU/mL at Week 24 or later.Robust T cell responses were observed to all VTP-300 encoded antigens.There were no Serious Adverse Events (SAEs), Grade 3 or 4 Adverse Events (AEs) related to treatment. Interim IM-PROVE II data: imdusiran and VTP-300 Interim data from the IM-PROVE II clinical trial showed; 20% of participants had undetectable HBsAg at Week 72 in the VTP-300 treatment group, compared to none in the placebo group.84% of participants in the VTP-300 treatment group were eligible for NUC discontinuation, compared to 52% in the placebo group.88% of those who did discontinue remained off NUCs, compared to 80% in the placebo group remaining off NUCs at time of data cutoff on April 12, 2024.Robust reductions of HBsAg were observed during the imdusiran lead-in period with 95% of participants achieving HBsAg <100 IU/mL before undergoing dosing in the VTP-300 treatment or placebo groups at week 24. A statistically significant difference (p<0.05) in HBsAg levels between the VTP-300 treatment and placebo groups was recorded at Week 72.Treatment with imdusiran and VTP-300 was generally well-tolerated, with no SAEs or treatment discontinuations reported. Corporate Updates On June 3, 2024, Dr. Leon Hooftman joined the Company as Chief Medical Officer. He brings significant drug development expertise across a broad array of therapeutic areas including immunology, autoimmunity, hematology, oncology and infectious diseases. In June 2024, we announced a strategic pipeline prioritization following the positive interim data from VTP-300 in CHB presented at EASL. This announcement included the prioritization of the development of VTP-300 in CHB and VTP-1000 in celiac disease, and consequently a reduction in workforce. Upcoming Milestones In the third quarter of 2024, the Company expects to: VTP-1000 (Celiac Disease): Dose the first patient in GLU001, a randomized, placebo-controlled Phase 1 trial including a controlled gluten challenge to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000 in adults with celiac disease. In the fourth quarter of 2024, the Company expects to: VTP-300 (HBV): Announce updated interim data from HBV003, our Phase 2b trial evaluating additional dosing of VTP-300 and timing of PD-1 inhibition, in people with CHB on NUC therapy.Announce updated interim data from the Phase 2a AB-729-202 clinical trial evaluating the combination of VTP-300 and Arbutus’ imdusiran, in people with CHB on NUC therapy. Pipeline These are estimated timelines only and our pipeline may be subject to change. Second Quarter 2024 Financial Highlights Cash position: As of June 30, 2024, cash, cash equivalents and restricted cash were $117.8 million, compared to $130.0 million as of March 31, 2024. The net cash used in operating activities was $12.0 million in the second quarter of 2024, primarily resulting from development of our pipeline and ongoing clinical trials offset by receipt of an R&D tax credit of $1.4 million. Based on current research and development plans, the Company expects its available resources to fund its operating expenses and capital expenditure requirements into the second quarter of 2026.Research and development expenses: Research and development expenses were $11.7 million in the second quarter of 2024 compared to $11.1 million in the first quarter of 2024, with the increase mainly attributable to the progression of VTP-300 (HBV) through the two ongoing Phase 2 trials, partially offset by a reduction in expense from VTP-200 (HPV) which completed in the first quarter of 2024 and for which data was presented in April 2024. The quarter-on-quarter R&D expense per program is outlined in the following table. Period ended Three monthsended June30, 2024 Three monthsended March31, 2024 Change $000 $000 $000 Direct research and development expenses by program: VTP-200 HPV $383 $1,253 $(870)VTP-300 HBV 3,034 1,913 1,121 VTP-500 MERS1 304 172 132 VTP-600 NSCLC2 24 164 (140)VTP-850 Prostate cancer 414 178 236 VTP-1000 Celiac 1,371 1,374 (3)Other and earlier stage programs 908 784 124 Total direct research and development expenses $6,438 $5,838 $600 Indirect research and development expenses: Personnel-related (including share-based compensation) 4,763 4,335 428 Facility related 342 390 (48)Other indirect costs 119 562 (443)Total indirect research and development expenses 5,224 5,287 (63)Total research and development expense $11,662 $11,125 $537 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 Phase 1/2a trial is sponsored by Cancer Research UK. General and administrative expenses: General and administrative expenses were $7.2 million in the second quarter of 2024, compared to $6.0 million in the first quarter of 2024. The increase of $1.2 million relates primarily to a loss of $0.1 million on foreign exchange in the second quarter of 2024, compared to a gain of $1.2 million in the first quarter of 2024.Net loss: For the second quarter of 2024, the Company generated a net loss attributable to its shareholders of $16.9 million, or $(0.43) per share on both basic and fully diluted bases, compared to a net loss attributable to its shareholders of $15.5 million, or $(0.40) per share on both basic and fully diluted bases in the first quarter of 2024. About Barinthus Bio Barinthus Bio is a clinical-stage biopharmaceutical company developing novel T cell 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 product candidates in infectious disease and autoimmunity, including: VTP-300, an immunotherapeutic candidate utilizing our ChAdOx/MVA platform designed as a potential component of a functional cure for chronic HBV infection and VTP-1000, an autoimmune candidate designed to utilize the SNAP-Tolerance Immunotherapy (TI) platform to treat patients with celiac disease. Barinthus Bio also has a Phase 1 clinical trial for VTP-850, a second-generation immunotherapeutic candidate designed to treat recurrent prostate cancer. Barinthus Bio’s proven scientific expertise, diverse portfolio and focus on pipeline development uniquely positions the company to navigate towards delivering treatments for people with infectious diseases and autoimmunity that have a significant impact on their everyday lives. For more information, visit www.barinthusbio.com. 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, the timing for initiation of any clinical trials, including dosing of the first patient in GLU001 for VTP-1000, our anticipated regulatory filings and approvals, our cash runway, 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) June 30,2024 December 31,2023ASSETS Cash, cash equivalents and restricted cash$117,774 $142,090 Research and development incentives receivable 4,523 4,908 Prepaid expenses and other current assets 9,582 9,907 Total current assets 131,879 156,905 Goodwill 12,209 12,209 Property and equipment, net 10,962 11,821 Intangible assets, net 23,527 25,108 Right of use assets, net 7,286 7,581 Other assets 886 882 Total assets$186,749 $214,506 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable 2,556 1,601 Accrued expenses and other current liabilities 10,278 9,212 Deferred income 839 — Operating lease liability - current 1,916 1,785 Total current liabilities 15,589 12,598 Non-current liabilities: Operating lease liability - non-current 10,654 11,191 Contingent consideration 1,888 1,823 Other non-current liabilities 1,338 1,325 Deferred tax liability, net 490 574 Total liabilities$29,959 $27,511 Commitments and contingencies (Note 15) Stockholders’ equity: Ordinary shares, £0.000025 nominal value; 39,184,338 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 390,273 386,602 Accumulated deficit (209,010) (176,590)Accumulated other comprehensive loss – foreign currency translation adjustments (24,732) (23,315)Total stockholders’ equity attributable to Barinthus Biotherapeutics plc shareholders 156,618 186,784 Noncontrolling interest 172 211 Total stockholders’ equity$156,790 $186,995 Total liabilities and stockholders’ equity$186,749 $214,506 BARINTHUS BIOTHERAPEUTICS PLC CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (IN THOUSANDS, EXCEPT NUMBER OF SHARES AND PER SHARE AMOUNTS) (UNAUDITED) Three months ended Six months ended June 30, 2024 June 30, 2023 June 30, 2024 June 30, 2023License revenue 1$— $334 $— $802 Total revenue — 334 — 802 Operating expenses Research and development 11,662 13,543 22,787 23,357 General and administrative 7,201 13,128 13,195 25,266 Total operating expenses 18,863 26,671 35,982 48,623 Other operating income 577 — 782 — Loss from operations (18,286) (26,337) (35,200) (47,821)Other income/(expense): Interest income 635 522 1,410 2,110 Interest expense (12) (14) (24) (14)Research and development incentives 693 559 1,287 1,716 Other income 20 310 20 310 Total other income, net 1,336 1,377 2,693 4,122 Loss before income tax (16,950) (24,960) (32,507) (43,699)Tax benefit 7 1,136 44 1,652 Net loss (16,943) (23,824) (32,463) (42,047)Net loss attributable to noncontrolling interest 12 22 43 65 Net loss attributable to Barinthus Biotherapeutics plc shareholders (16,931) (23,802) (32,420) (41,982) Weighted-average ordinary shares outstanding, basic 39,041,111 38,407,672 38,907,296 38,211,625 Weighted-average ordinary shares outstanding, diluted 39,041,111 38,407,672 38,907,296 38,211,625 Net loss per share attributable to ordinary shareholders, basic$(0.43) $(0.62) $(0.83) $(1.10)Net loss per share attributable to ordinary shareholders, diluted$(0.43) $(0.62) $(0.83) $(1.10) Net loss$(16,943) $(23,824) $(32,463) $(42,047)Other comprehensive gain/(loss) – foreign currency translation adjustments 164 5,604 (1,413) 10,184 Comprehensive loss (16,779) (18,220) (33,876) (31,863)Comprehensive loss attributable to noncontrolling interest 11 15 39 52 Comprehensive loss attributable to Barinthus Biotherapeutics plc shareholders$(16,768) $(18,205) $(33,837) $(31,811) 1 Includes license revenue from related parties for the three and six months ended June 30, 2024 of nil (three and six months ended June 30, 2023: $0.3 million 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 A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/c0677b65-29bb-4869-b045-22325fa94f17

Phase 2Phase 1Financial StatementImmunotherapyClinical Result

13 Jun 2024

·www.fiercebiotech.com

Barinthus lays off 25% of staff, sidelines prostate cancer program to stretch out cash

Barinthus Biotherapeutics expects a restructuring to stretch the company's cash runway into 2026. Barinthus Biotherapeutics has used positive interim data from a pair of phase 2 trials for its hepatitis B therapy as justification for sidelining its prostate cancer candidate and jettisoning a quarter of the T-cell-focused biotech’s workforce. The U.K.-based company—formerly known as Vaccitech—said the interim readouts from the trials of VTP-300 it unveiled at the European Association for the Study of the Liver (EASL) Congress last week “demonstrated VTP-300’s potential to significantly reduce and maintain hepatitis B surface antigen (HBsAg) levels and achieve undetectable HBsAg levels in patients with” chronic hepatitis B (CHB). At the time, analysts at William Blair said the “results demonstrate VTP-300's ability to potentially induce a functional cure for CHB, pending the outcome of further development.” In Wednesday’s postmarket release, Barinthus also pointed to “encouraging” preclinical findings for its lead candidate, a celiac disease drug called VTP-1000, as reason for prioritizing that asset along with VTP-300. VTP-1000 is designed to balance the immune response by inducing gluten-specific T regulatory cells and reduce gluten-specific T effector cell responses. After preclinical research in disease models demonstrated “mode of action and disease amelioration,” Barinthus said it is gearing up to take VTP-1000 into the clinic in the third quarter. “The company expects to undergo a restructuring to align resources with the streamlined pipeline, which will include a workforce reduction of approximately 25% and an estimated extension of the cash runway into the second quarter of 2026,” the company said in the June 12 release. The biotech had previously expected the $130 million in cash and equivalents it had to hand as of the end of March to run out by the end of 2025. An ongoing phase 1 trial of VTP-850 in prostate cancer will be completed, the company confirmed in yesterday’s release. But the immunotherapeutic, which encodes for multiple prostate-associated antigens, didn’t appear to feature in the company’s future plans as set out in the announcement. There was also no mention in the release of VTP-200, an immunotherapeutic combo regimen for high-risk human papillomavirus that hit the primary safety endpoint of a phase 1b/2 trial in April. However, the data for the trial’s overall patient population didn’t demonstrate a significant improvement in hrHPV clearance or cervical lesion clearance. “With this pipeline prioritization, we put the company in a strong position to maximize the probability of success, particularly given the encouraging VTP-300 phase 2 interim data presented at EASL earlier this month and the compelling differentiation of our novel SNAP-TI platform to treat autoimmune diseases,” CEO Bill Enright said in the release. “In line with our pipeline prioritization, we have made the difficult decision to reduce our workforce,” Enright added. “I would like to thank our talented employees for their contributions to the company’s achievements.” In a note this morning, analysts at William Blair gave their blessing to Barinthus’ move. “We agree with management’s decision to streamline the company’s R&D pipeline, which in our view is evidence-based and driven by evolving data,” the analysts wrote. “We believe new data generated from the VTP-300 program could showcase the regimen’s role in helping patients living with CHB to achieve functional cures.”

Phase 2Phase 1Immunotherapy

100 Deals associated with VTP-200

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Indication	Highest Phase	Country/Location	Organization	Date
Human Papillomavirus Infection	Phase 2	BE	Vaccitech (UK) Ltd.	16 Mar 2021
Human Papillomavirus Infection	Phase 2	EE	Vaccitech (UK) Ltd.	16 Mar 2021
Uterine Cervical Dysplasia	Phase 2	BE	Vaccitech (UK) Ltd.	16 Mar 2021
Uterine Cervical Dysplasia	Phase 2	EE	Vaccitech (UK) Ltd.	16 Mar 2021
Uterine Cervical Dysplasia	Phase 2	GB	Vaccitech (UK) Ltd.	16 Mar 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NEWS Manual	Phase 1/2	Human Papillomavirus Infection	108	VTP-200	mnvhljyurs(ihmawztetr) = Pooled data from the five different active dose groups did not demonstrate a statistically significant improvement in either high-risk HPV or cervical lesion clearance rates compared to placebo. uhhcygplpl (hstxkqhokt )	Negative	20 Apr 2024
				Placebo
NCT04607850 (APOLLO, Corporate Publications) Manual	Phase 1/2	Human Papillomavirus Infection	108	Placebo	clugdrutpo(vikedijklo) = The APOLLO study met its primary safety endpoint, demonstrating that VTP-200 was generally well-tolerated and was administered with no treatment-related grade 3 or higher unsolicited AEs and no treatment-related SAEs. evcdinivfv (paeivznjer ) Met	Positive	18 Apr 2024
				VTP-200 (mid dose+low dose)

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