Document

 
 
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
 
 
FORM 6-K
 
 
Report of Foreign Private Issuer
Pursuant to Rule 13a-16 or 15d-16
Under the Securities Exchange Act of 1934
For the month of August 2021
Commission File Number 001-40316
 
 
VECTIVBIO HOLDING AG
(Exact name of registrant as specified in its charter)
 
 

Aeschenvorstadt 36
4051 Basel
Switzerland
(Address of principal executive offices)
 
 
Indicate by check mark whether the registrant files or will file annual reports under cover Form 20-F or Form 40-F.
Form 20-F Form 40-F
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):
 
 



On August 31, 2021, VectivBio Holding AG, or the Company, issued a press release announcing that the Company has entered into a definitive agreement to acquire Comet Therapeutics, Inc., or Comet Therapeutics. Under the terms of the agreement, the Company will acquire Comet Therapeutics in exchange for equity and cash payable at closing as well as additional equity or cash payments upon the achievement of certain specified future development milestones. The press release also announced that the Company will host an R&D Day for investors and analysts on September 21, 2021. A copy of the press release is furnished as Exhibit 99.1 hereto.

On August 31, 2021, the Company also released an updated presentation to be used from time to time in meetings with potential and current investors. A copy of the presentation is furnished as Exhibit 99.2 hereto.


Exhibits  
99.1 
99.2





SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
 
  VECTIVBIO HOLDING AG

August 31, 2021
  

By:
 /s/ Claudia D’Augusta
   Claudia D’Augusta
   Chief Financial Officer


Document

VectivBio to Acquire Comet Therapeutics and Host R&D Day
- Acquisition of Innovative Small Molecule Platform Significantly Expands Rare Disease Pipeline -
- VectivBio to Host R&D Day on September 21, 2021-

BASEL, Switzerland, August 31, 2021 (GLOBE NEWSWIRE) -- VectivBio Holding AG (“VectivBio”) (Nasdaq: VECT), a clinical-stage biopharmaceutical company pioneering novel transformational treatments for severe rare conditions, today announced that it will acquire Comet Therapeutics, Inc., a privately held company that has been developing drugs to address previously untreatable Inherited Metabolic Diseases. This acquisition significantly expands VectivBio’s rare disease pipeline.

The novel and proprietary CoMET platform is aimed at addressing Inherited Metabolic Diseases (IMDs) with deficit of energy metabolism and depletion of functional Coenzyme A (“CoA”)
IMDs affect over 75,000 patients in the US and Europe and are a significant cause of mortality in infants and young people
This modular technology has the potential to address multiple previously untreatable IMDs by targeting the key cellular dysfunctions that underlie these conditions. This approach would overcome important limitations of standard of care and has the potential to prevent the clinical progression of IMDs
The CoMET platform leverages innovative chemistry with the goal of providing a stabilized CoA precursor and key metabolic intermediates to restore fundamental cellular metabolism
Four distinct programs are currently in research, with plans to enter the clinic with the first program in the next 18 months

VectivBio has entered into a definitive agreement to acquire Comet Therapeutics, a biotechnology company that has been developing a small molecule platform for the treatment of a large group of IMDs that occur in approximately 1 in 800 births. Under the terms of the agreement, VectivBio will acquire Comet Therapeutics in exchange for equity and cash payable at closing, as well as additional equity or cash payments upon the achievement of certain specified future development milestones. The board of directors of both companies have unanimously approved the transaction.

IMDs are severe rare genetic disorders caused by congenital defects of metabolism fundamental to energy generation and the survival of cells. In addition to disrupted energy production and the accumulation of toxic metabolites, these defects cause dysregulation of CoA, a core component of many metabolic pathways. As a result, IMDs are often fatal or highly life-impairing conditions that primarily affect children and currently have limited effective treatment options. We believe that the modular CoMET platform holds the potential to treat a wide variety of rare metabolic diseases by generating medicines that restore cellular metabolism.

The foundation of the proprietary technology is a stabilized CoA precursor backbone that has been shown in preclinical studies to supply functional CoA and carry tailored intermediary metabolite cargos. The modular technology targets multiple groups of IMDs that share a common metabolic pathway, independent of underlying genetic mutation. These include severe life-threatening disorders such as methylmalonic acidemia (MMA) and propionic acidemia (PA). Importantly, in preclinical studies this technology has demonstrated the ability to provide both CoA and intermediate metabolites to all relevant organ systems affected by IMDs, including the liver, muscle and brain, thus bearing the potential to overcome some of the delivery limitations of other therapeutic approaches currently in development.




“The acquisition of the CoMET platform is in line with our core mission of developing disease-modifying treatments for rare severe diseases,” said Luca Santarelli, M.D., Founder and Chief Executive Officer of VectivBio. “The platform’s potential to deliver a pipeline of medicines that target the fundamental molecular pathophysiology of IMDs by unlocking previously inaccessible pathways, would provide us with the opportunity to transform the lives of these patients. We are eager to begin work on our new programs and look forward to progressing our first candidate towards the clinic.”

The transaction is expected to close by the end of September 2021, subject to customary closing conditions. Comet Therapeutics’ current investors include Sofinnova Partners, INKEF Capital, Canaan and Mission BioCapital.

VectivBio to Host R&D Day on September 21, 2021

VectivBio will host an R&D Day for investors and analysts on Tuesday, September 21, 2021. The virtual event will take place from 10:00 a.m. to 12:00 p.m. EDT.

Topics to be addressed during the presentation include apraglutide’s development and potential in treating Short Bowel Syndrome with Intestinal Failure and Graft-versus-Host-Disease, and an overview of the Company’s new CoMET platform.

Members of VectivBio’s management team will be joined by external experts: Kishore Iyer, MBBS, Director of Adult and Pediatric Intestinal Rehabilitation & Transplantation at Mount Sinai Medical Center; and Robert Zeiser, M.D., Head of Tumor Immunology and Immune Modulation at the University Medical Center Freiburg.

The live webcast of the presentation and the question-and-answer session will be accessible by visiting the “Events and Presentations” section of VectivBio’s website at https://ir.vectivbio.com/events-and-presentations. A dial-in number will also be provided closer to the event.

About VectivBio

VectivBio (Nasdaq: VECT) is a global, clinical-stage biotechnology company focused on the discovery, development and commercialization of innovative treatments for severe rare conditions. VectivBio is committed to pursuing product candidates with a clear mechanism of action and the potential to meaningfully transform and improve the lives of patients and their families. VectivBio’s lead product candidate, apraglutide, is a next-generation GLP-2 analog being developed as a differentiated therapeutic for a range of rare gastrointestinal diseases. Apraglutide is currently being evaluated in a global Phase 3 clinical trial as a once-weekly treatment for short bowel syndrome with intestinal failure. VectivBio also plans to initiate clinical studies of apraglutide in additional indications, including graft versus host disease, where GLP-2 is believed to be central to disease pathophysiology.

Forward Looking Statements

Forward-looking statements are statements that are not historical facts. Words and phrases such as “anticipated,” “forward,” “will,” “would,” “may,” “remain,” “potential,” “prepare,” “expected,” “believe,” “plan,” “near future,” “belief,” “guidance,” and similar expressions are intended to identify forward-looking statements. These statements include, but are not limited to, statements concerning the consummation of the acquisition of Comet Therapeutics and the prospects of its platform, the success of development and commercialization efforts with respect to VectivBio’s product candidate



and VectivBio’s plans to initiate additional clinical studies of apraglutide and to expand its rare disease product portfolio. All of such statements are subject to risks and uncertainties, many of which are difficult to predict and generally beyond VectivBio’s control, that could cause actual results to differ materially from those expressed in, or implied or projected by, the forward-looking statements. Such risks and uncertainties include, but are not limited to: the ability to satisfy the closing conditions and consummate the acquisition of Comet Therapeutics, the impacts of the ongoing COVID-19 pandemic, including interruptions or other adverse effects on clinical trials and delays in regulatory review; delay in or failure to obtain regulatory approval of VectivBio’s product candidate and successful compliance with FDA and other governmental regulations applicable to product approvals; the risks inherent in drug development and in conducting clinical trials; and those risks and uncertainties identified in the “Risk Factors” section of VectivBio’s Registration Statement on Form F-1 declared effective by the Securities and Exchange Commission on April 8, 2021 and its other subsequent filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, VectivBio undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

For more information visit www.vectivbio.com, and follow us on LinkedIn.

Investors
Graham Morrell
graham.morrell@vectivbio.com

Media
Morgan Warners
+1 (202) 295 0124
morgan.warners@fgh.com



vectivbio-corppresx31aug
Transformational Therapies for Rare Conditions August 2021 CONFIDENTIAL


 
Corporate Presentation This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that reflect the current beliefs, expectations and assumptions of VectivBio Holding AG (the “Company,” “we” or “our”) regarding the future of its business, its future plans and strategies, clinical results, future financial condition and other future conditions. All statements other than statements of historical facts contained in this presentation, including statements regarding future results of operations and financial position, business strategy, product candidates, planned preclinical studies and clinical trials, results of clinical trials, research and development costs, regulatory approvals, timing and likelihood of success, as well as plans and objectives of management for future operations, are forward-looking statements. The words “may,” “will,” “expect,” “anticipate,” “aim,” “estimate,” “intend,” “plan,” “believe,” “is/are likely to,” “potential,” or “continue” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: the ability of our clinical trials to demonstrate acceptable safety and efficacy of our product candidate; the timing, progress and results of clinical trials for our product candidate, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work, the period during which the results of the trials will become available, and our research and development programs; the timing, scope and likelihood of regulatory filings and approvals; our ability to obtain marketing approvals of our product candidate and to meet existing or future regulatory standards or comply with post-approval requirements; our expectations regarding our ability to fund our operating expenses and capital expenditure requirements with our cash and cash equivalents and net proceeds of this offering; future milestone or royalty payments to our licensing partners or other third- parties, and the expected timing of such payments; our expectations regarding the potential market size and the size of the patient populations for our product candidate, if approved for commercial use; our expectations regarding the potential advantages of our product candidate over existing therapies for SBS-IF and our expectations regarding potential uses of our product candidate to treat other indications; the success of development and commercialization of the CoMET platform; our ability to develop new product candidates using the CoMET platform; developments and projections relating to our competitors and our industry, including competing therapies; the impact of COVID-19 on our business, operations and prospects and on our clinical trials; our potential to enter into new collaborations; our expectations with regard to our ability to develop additional product candidates or leverage our current product candidate for other indications, and our ability to identify additional products, product candidates or technologies with significant commercial potential that are consistent with our commercial objectives; our ability to develop, acquire and advance additional product candidates into, and successfully complete, clinical trials; the commercialization and market acceptance of our product candidate; our marketing and manufacturing capabilities or those of third parties with which we contract; our ability to operate our businesses without infringing the intellectual property rights and proprietary technology of third parties; the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates; estimates of our expenses, future revenue, capital requirements, our needs for additional financing and our ability to obtain additional capital; regulatory development in the United States, Europe and other jurisdictions; and other risks described in the “Risk Factors” section of our Registration Statement on Form F-1 declared effective by the Securities and Exchange Commission (SEC) on April 8, 2021 and our other subsequent filings with the SEC. The forward-looking statements in this presentation represent our views as of the date of this presentation. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. New risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. We file Current Reports on Form 6-K, Annual Reports on Form 20-F, and other documents with the SEC. You should read these documents for more complete information about us. You may obtain these documents for free by visiting EDGAR on the SEC website at www.sec.gov. This presentation concerns products that are under clinical investigation and which have not yet been approved for marketing by the relevant regulatory authorities. They are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. Disclaimer and Forward-Looking Statements 2


 
Corporate Presentation Building a Fully Integrated Global Rare Disease Company Apraglutide in SBS-IF: an underserved market demanding better products with >$2B potential *Gattex® (teduglutide), known as Revestive® outside the U.S. SBS-IF: Short Bowel Syndrome Intestinal Failure; SOC: Standard of Care; MOA: Mechanism of Action • Designed to address previously intractable Inherited Metabolic Diseases and prevent clinical progression of IMDs • Modular chemistry designed to restore fundamental cellular metabolism • 4 programs in research, plans to enter the clinic in 18 months • Apraglutide, a differentiated drug candidate for Short Bowel Syndrome • >$2B market potential, severely underserved • Gattex®*, only approved product with several shortcomings and limited penetration • Apraglutide offers a next generation profile and the potential to establish a new SOC • MOA and approval path are validated • Multiple life-cycle opportunities • Successful rare disease track record in R&D, Commercial and Business Development • Expertise across multiple disease areas and modalities • Strong focus on execution and discipline in asset selection Transformative CoMET platform Successful Team Compelling Ph3 Asset 3


 
Corporate Presentation World Class Management Team with Track Record of Success Claudia D’Augusta, Ph.D. Chief Financial Officer Alain Bernard, Ph.D. Chief Technology Officer Kevin Harris, MBA Chief Commercial Officer Christian Meyer, M.D., Ph.D. Chief Operating Officer Sarah Holland, Ph.D., MBA Chief Business Officer Luca Santarelli, M.D. Founder Chief Executive Officer Significant drug development and commercialization expertise in rare diseases Omar Khwaja, M.D., Ph.D Chief Medical Officer 4


 
Corporate Presentation5 VectivBio: Key Company Facts and 2021 accomplishments (to date) * Includes $146.6M in gross proceeds from Initial Public Offering and $7.5M pursuant to a simple agreement for future equity (SAFE) with an existing shareholder; net proceeds after underwriting discount, commissions and fees of $140.5M ** Unaudited; Cash balance on December 31st, 2020: $40.2M Founded in 2019, based in Switzerland and on the US Raised $154M* in Nasdaq IPO (VECT) on April 9, 2021 Cash and Cash Equivalents as of June 30, 2021: $144.6M** Accomplishments in 2021 Apraglutide: • Ph3 programs started in SBS – • STARS trial initiated in January • STARS Extend trial initiated in July • STARS Nutrition trial initiated in June • ODD status obtained in GVHD - Ph2 trial in preparation Pipeline expansion: • CoMET platform acquired – 4 programs added to the pipeline


 
Corporate Presentation Our Pipeline Indication(s) Stage of Development Upcoming Milestone(s) Adult SBS-IF Pediatric SBS-IF1 • Intend to initiate Ph 3 in 2023 Acute Graft Versus Host Disease1 • Intend to initiate Ph 2 in Q1 2022 Preclinical Phase 1 Phase 2 Phase 3 Apraglutide Discovery • First readout: H1 2022 • Top-line results: H2 2023 • OLE VB-1197 VB-1200 VB-1300 VB-1400 CoMET Malonic and Propionic Acidemia Other Organic Acidemias VB-1197 • Intend to initiate Ph 1 by Q1 2023 Urea Cycle Disorders Fatty Acid Oxidation Disorders Amino Acidopathies 6 1. Our planned pediatric SBS-IF and acute graft versus host disease clinical trials rely on clinical trial data from our completed healthy volunteer Phase 1 and adult SBS-IF patient Phase 2 clinical trials. To date, we have not completed any dedicated clinical trials in pediatric SBS-IF and acute graft versus host disease.


 
Short Bowel Syndrome with Intestinal Failure (SBS-IF)


 
Corporate Presentation Short Bowel Syndrome (SBS) A severe rare condition with a burdensome standard of care 1. Pironi L et al. Clin Nutr. 2016; 2. Gattex® (teduglutide) for injection. Prescribing Information; 3. Revestive® Summary of Product Characteristics. IBD: Irritable Bowel Disease • SBS results from extensive intestinal resection due to IBD, trauma, mesenteric infarction, bariatric surgery, etc.1 • SBS Intestinal Failure (SBS-IF) requires life-long, burdensome parenteral support (PS)1 Nutritional Support and Concomitant Medications Gattex® / Revestive® (only GLP-2 analog approved for SBS-IF)2,3 Increases intestinal absorption and reduces the volume of parenteral support Parenteral Support (PS) Pre-Surgery Post-Surgery Standard of Care Approved in 2012 8


 
Corporate Presentation SBS-IF is Associated with Significant Burden 1. Parrish CR et al. Gastroenterol Hepatol (N Y). 2017; 2. Billiauws L et al. J Visc Surg. 2018; 3. Schalamon J et al. Best Pract Res Clin Gastroenterol. 2003; 4. Howard L. Gastroenterology. 2006; 5. Ballinger R et al. ISPOR 2019; 6. Piamjariyakul U et al. Nurs Econ. 2010. PN: Parenteral Nutrition; QoL: Quality of Life High mortality rate for SBS patients on home parenteral nutrition • 30% after 5 years3 Central venous access complications1,2 Organ damage1,2 GI complications1,2 Significant reductions in patient QoL:4 Negative QoL impact on caregivers5 Average annual costs of chronic PN (including home care, PN, and hospitalizations)6 • $185-594k Significant indirect costs Significant Morbidity1,2 Reduced Quality of Life1,4,5 Burden to the Healthcare System6 Increased Mortality1,31 2 3 4 9


 
Corporate Presentation SBS-IF Represents a Significant Opportunity We believe there is a peak market potential >$2 billion * We estimate that the addressable global market opportunity for apraglutide, if approved, in SBS-IF, could exceed $2 billion per year through significant growth in the number of eligible patients receiving a GLP-2 analog, potentially improved compliance and persistency, and geographic expansion beyond where teduglutide is approved today. Source: Custom market research commissioned by VectivBio, Nov 2019; internal estimates. Rest of World Opportunity ~ 1,000 SBS-IF patients in Japan China Other Markets 5,000 7,500 2,500 7,500 U.S. Market Opportunity EU Market Opportunity We Believe There is a >$2 Billion Peak Market Potential Opportunity* Est. Peak SBS-IF Patients Treated with GLP-2 U.S. and EU Market Opportunity Est. SBS-IF Patients 10


 
Corporate Presentation Significant Unmet Medical Needs Remain with Gattex Limited/niched use, sub-optimal persistency 1. Gattex® (teduglutide) for injection. Prescribing Information; 2. Gattex® (teduglutide) Instructions for Use; 3. Jeppesen PB, et al. Gastroenterology. 2012; 4. Jeppesen PB et al. Clin. Nutr. 2013; 5. Jeppesen PB, et al. Gastroenterology. 2018; 6. CRA Market Research, Nov 2019 (U.S. and EU5); 7. Symphony Health, PatientSource®, Dec 2015–Jan 2019 (analysis period of claims); patient cohort: U.S. patients starting Gattex who have had an SBS diagnosis and at least 180 days of parenteral nutrition prior to receiving Gattex and who could be followed for at least 24 months; patients are considered discontinued if they have a gap in therapy >90 days; patients are considered persistent until first event of discontinuation. Limitations of Gattex • 2hr half life, daily subcutaneous injections1 • Lengthy and complex administration procedure2 • Only partially addresses the needs of SBS-IF patients: • Adverse events: injection site reactions and abdominal pain1,3 • No demonstrated impact on patients’ quality of life4 • Colon-in-continuity patients treated with Gattex did not exhibit a significant reduction in PS volume as compared to placebo- treated patients in Phase 3 trial5 • Gattex is predominantly used in stoma/high PS SBS-IF patients6 Gattex 24-Month Persistency, U.S. (n=194)7 74% 62% 48% 34% 0% 20% 40% 60% 80% 100% 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Months 11


 
Corporate Presentation12 Apraglutide Has the Potential to Establish a New Standard of Care *Management expectations, based on clinical trials to date. 1. Martchenko SE et al. J Pharmacol Exp Ther. 2020; 2. Hargrove DM et al. J Pharmacol Exp Ther. 2020; 3. Eliasson J et al. Clinical Nutrition ESPEN 40 (2020), 459; 4. Eliasson J et al. Clinical Nutrition ESPEN 40 (2020), 436. Enhanced Value Proposition Differentiated Apraglutide Target Profile* • Demonstrated robust pharmacology • Improved intestinotrophic effects in preclinical models1,2 • Enhanced energy absorption in SBS patients in Phase 23 • Differentiated clinical and regulatory strategy in Phase 3 • Takes into account remnant bowel anatomy when weaning PS and assessing benefits from GLP-2 treatment • Focuses on clinically meaningful effects, including enteral autonomy and quality of life measurements • Convenient administration • Weekly dosing3,4 • Developing pre-filled syringe


 
Corporate Presentation Apraglutide Designed to Have Superior PK/PD vs. Other GLP-2s Comparative peptide sequence of apraglutide to teduglutide and glepaglutide Source: Adapted from K Wisńiewski et al., J. Med. Chem. 2016, 59, 3129−3139 Molecular class: Peptide, chemically synthesized Chemical name: [Gly2, Nle10, D-Phe11, Leu16]hGLP-2 (1-33)-NH2 Structural formula: H-His-Gly-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Nle-D-Phe-Thr-Ile-Leu-Asp-Leu-Leu-Ala-Ala-Arg-Asp-Phe-Ile- Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-NH2 (Sodium salt) The sequence of apraglutide contains one D stereoisomer-amino acid (D-phenylalanine) and two achiral amino acids (glycine). All other amino acids are of L-configuration. Apraglutide is synthesized as a single enantiomer with all stereo-centers of defined chirality Replacement of two asparagines, Asn11 by D-Phe11 and Asn16 by Leu16, causes a significant change in plasma protein binding and corresponding remarkable decrease in total clearance. (K Wisńiewski et al.) Replacement of Met10 by Nle10 provides enhanced chemical stability. (K Wisńiewski et al.) The lower charge due to the amide group is thought to result in a more limited solubility, thereby slowing down the absorption from the SC injection site into the circulation and increasing the terminal half-life. Gly2 eliminates enzymatic cleavage by DPP-IV enzyme. (K Wisńiewski et al.) AA Pos. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 Native GLP-2 H A D G S F S D E M N T I L D N L A A R D F I N W L I Q T K I T D Teduglutide H G D G S F S D E M N T I L D N L A A R D F I N W L I Q T K I T D Glepaglutide H G E G T F S S E L A T I L D A L A A R D F I A W L I A T K I T D K Apraglutide H G D G S F S D E Nle D-Phe T I L D L L A A R D F I N W L I Q T K I T D Chemical Name and Structure 34+ OH OH K K K K K K NH2 NH2 13


 
Corporate Presentation Apraglutide Possesses Differentiated Pharmacology (1/2) Pharmacokinetic comparisons vs. teduglutide and glepaglutide1 1. Hargrove DM et al. J Pharmacol Exp Ther. 2020; 2. Bolognani F et al. ESPEN 2020. Human Rat 1 10 1,000 10,000 90 120 Pl as m a C on ce nt ra tio n (n g/ m l) 60 Time (min) hGLP-2 Teduglutide Glepaglutide Apraglutide 100 300 Apraglutide Half Life (T1/2) 70–72 hours2 Manufacturing Synthetic PK supports weekly dosing 14


 
Corporate Presentation Apraglutide Possesses Differentiated Pharmacology (2/2) Greater efficacy on intestinal growth in head-to-head preclinical studies in rats * = p< 0.05 vs corresponding vehicle control. ^ = p< 0.05 vs. corresponding apraglutide treatment group. Source: Hargrove et al. J Pharmacol Exp Ther. 2020. Daily Injection (24 hrs. Dosing Interval) Intestine weight 96 hours post 1st injection Single Injection Intestine weight 72 hours post injection 60 50 40 30 20 10 0 30 nmol/kg 300 nmol/kg Sm al l I nt es tin e W et W ei gh t (% in cr ea se o ve rv eh ic le ) * * ^ * ^ * ^ * ^ * -10 0 10 20 30 30 nmol/kg 300 nmol/kg Sm al l I nt es tin e W et W ei gh t (% in cr ea se o ve rv eh ic le ) * ^ ^ ^ * ^ * Apraglutide Teduglutide Glepaglutide 15


 
Corporate Presentation Saline Apraglutide GLP-2 Activation by Apraglutide Significantly Increased Intestinal Mucosal Mass and Length Source: Slim et. al., J Parenter Enteral Nutr., 2018; Data on file. VectivBio. Basel, Switzerland. ln te st in e le ng th (c m ) 20 15 10 5 0 -5 -10 -15 Representative samples of jejunum from JC piglets (magnification = 20X) ApraglutideVehicle M uc os al M as s( m g/ cm ) 210 190 170 150 130 110 90 Change in Intestinal Length Change in Mucosal Mass Histological observations of the jejunum in apraglutide-treated jejunostomy piglets demonstrated elongated villi compared to control 16


 
Corporate Presentation Phase 2 Program Two studies established proof of concept and confirmed weekly dosing 1. Eliasson J et al. Clinical Nutrition ESPEN 40 (2020), 459; 2. Eliasson J et al. Clinical Nutrition ESPEN 40 (2020), 436. GLY-311: SBS Safety Study2 N=8 GLY-321: SBS Metabolic Balance1 N=8 Assessment of 5 mg/week apraglutide on safety, urine production, fecal wet weight and energy absorption Assessment of placebo, 5 and 10 mg/week apraglutide on safety and urine production Phase 2 Studies 17


 
Corporate Presentation Study GLY-321: Once-Weekly Proof of Concept Achieved in SBS Clinically relevant pharmacodynamic effects observed in ALL subjects at 5 mg/week Source: Data on file. VectivBio. Basil, Switzerland. SEM: Standard Error of Mean Urinary Output Wet Weight Absorption Energy Absorption 0 200 400 600 800 1,000 Baseline End of Treatment C ha ng e fr om B as el in e, g /d ay Mean +/- SEM 0 200 400 600 800 1,000 Baseline End of Treatment C ha ng e fr om B as el in e, g /d ay Mean +/- SEM 0 250 500 750 1,000 1,250 1,500 Baseline End of Treatment C ha ng e fr om B as el in e, k J/ da y Mean +/- SEM 18


 
Corporate Presentation Apraglutide Studied in a Metabolic Balance Trial Apraglutide demonstrated statistically significant increases in energy absorption with weekly dosing *p=0.0374, **p=0.0150, ***p=0.0236 1. Eliasson J et al. Clinical Nutrition ESPEN 40 (2020), 459; 2. Jeppesen PB et al. Gut. 2005; 3. Naimi RM et al. Lancet Gastroenterol Hepatol. 2019. CFB: Change from Baseline Apraglutide1 5 mg ONCE-WEEKLY Urinary Output (% CFB) 39.1%* Wet Weight Absorption (CFB) 740.7 g/day** Energy Absorption (CFB) 1,094.8 kj/day*** • Only GLP-2 to demonstrate robust absorption enhancements after weekly dosing • Only GLP-2 to demonstrate statistically significant enhancement in energy absorption in Phase 22,3 • Enhanced energy absorption could result in better outcomes in patients 19


 
Corporate Presentation Phase 2 Safety: Apraglutide Generally Well-Tolerated All drug-related adverse events were expected based on the GLP-2 mechanism of action AE: Adverse Event; SAE: Serious Adverse Event Data on File, VectivBio, Basel (Switzerland) Study 321 4-wk Treatment Study (N=8) Study 311 3x 4-wk Treatment Study (N=8) Total AEs 80 157 Intensity: Mild 65 132 Not/unlikely related SAEs 3 8 Related SAEs 1 (abdominal pain) 0 20


 
Corporate Presentation Stoma Colon-in-Continuity (CIC) Prevalence2 ~45% of Patients ~55% of Patients Absorption deficits Fluids and nutrients Mainly nutrients PS requirements Fluids + nutrients = high PS volume Mainly nutrients = lower PS volume Response to Gattex*1 Robust effect on PS volume reduction Minimal effect on PS volume reduction SBS is Heterogeneous Based on Remnant Bowel Anatomy Stoma and CIC patients have different responses to Gattex1 *As compared to placebo at six months in the phase 3 study 1. Jeppesen PB et al. Gastroenterology. 2018; 2. Company Phase 3 feasibility and CRA Market Research, Nov 2019 (U.S. and EU5). Duodenum Jejunocolonic Anastomosis Jejunum Colon Duodenum Jejunum Stoma (on abdominal surface) Stoma Bag Adapted from: Jeppesen P et. al., Gastroenterology, 2018 21


 
Corporate Presentation Key Learnings from Past SBS Experience Inform Phase 3 Strategy Opportunity to improve outcomes by considering an individual’s remnant bowel anatomy 1. Jeppesen PB et al. Gastroenterology. 2018; 2. Joly F et al. Clin Nutr. 2020. Adapted from: Jeppesen P et. al., Gastroenterology, 2018 + Diuresis Nutrients Measure GLP-2 effects based on remnant bowel anatomy Diuresis Stoma CIC How to evaluate efficacy • Diuresis is a good marker of response in stoma patients • Diuresis proved insensitive1 in CIC patients; nutrient absorption must be considered2 How to establish clinical relevance • PS volume reduction has greatest therapeutic relevance in stoma patients • Days off and enteral autonomy are the therapeutic goals in CIC 22


 
Corporate Presentation23 STARS Study Design Pivotal Phase 3 study in SBS-IF patients Enrollment of 144 SBS-IF patients Week 24 • Primary endpoint: PS volume reduction • Secondary endpoints collected by anatomy Week 48 Secondary endpoints collected by anatomy Apraglutide (96 patients) Placebo (48 patients) 2:1 randomization Anatomy-specific randomization Two dose arms: weekly placebo and apraglutide (2.5 or 5 mg depending on body weight) Primary endpoint (week 24): PS volume reduction in overall population Secondary endpoints (week 24 and 48): Common and anatomy-specific Anatomy-specific PS reduction algorithm to best adapt PS requirements 1 2 3 4 5 6 First patient dosed January 2021; Topline results anticipated in 2H2023 Regulatory alignment obtained from FDA, EMA and PMDA on critical design elements


 
Corporate Presentation Lessons From the Market Inform Commercialization Strategy Source: Custom market research commissioned by VectivBio, Nov 2019; Custom market research commissioned by VectivBio, Nov 2019; Interviews with external experts. Most SBS patients are managed by GI generalists and not by SBS experts Strong and informative label for apraglutide to allow for promotional differentiation and clear product benefit messaging SBS is treated by a multidisciplinary care team requiring a tailored customer infrastructure VectivBio infrastructure mapped to patient journey and key touchpoints—prescribing, market access, and patient support Market Insight Our Strategy Patients, healthcare providers, and payers want products with a stronger value proposition Apraglutide properties and Phase 3 design aims to: • Deliver greater efficacy • Address disease heterogeneity • Establish clinical meaningfulness • Improve convenience 24


 
Corporate Presentation Key Predictive Treatment Variable Gattex Treatment Rate by Predictive Variable1 SBS Anatomy PS Frequency Per Week Drivers of Gattex Real World Utilization (U.S. and EU5) Gattex use is niched to stoma and to patients with high PS frequency Source: Custom market research commissioned by VectivBio, Nov 2019. 1. Does not account for market research overstatement. 28% 39% 53% 3 Days 4 Days 5–7 Days 46% 22% Stoma CIC Gattex is used by a factor of 2:1 in stoma patients in the U.S. 25


 
Corporate Presentation26 We Believe Apraglutide Can Significantly Expand the Market to >$2B There are multiple drivers that can establish apraglutide’s best-in-class value proposition G LP -2 R ev en ue 2019 GLP-2 Revenue Peak GLP-2 Revenue FY 2020 Market of ~$609M Potential Peak Market of >$2.0BDrivers of Market Growth Drivers of Apraglutide Use Improved convenience with weekly dosing Greater reduction in PS & enteral autonomy Consideration of remnant bowel anatomy Enhanced QoLImproved persistency (50% pts off Gattex @ 12 mos) Increased use in untreated patients (< ½ stoma and ¼ CIC pts on therapy) Expanded use outside the U.S. (only ~15% of sales ex-US) Global strategy


 
Acute Graft Versus Host Disease (GVHD)


 
Corporate Presentation Acute GVHD is a Life-Threatening Condition Resulting From Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Gastrointestinal GVHD is one of the leading causes of morbidity and mortality 1. Goker H et al. Exp Hematol. 2001; 2. D'Souza A et al. Blood Marrow Transplant. 2020; 3. Baldomero H et al. EBMT activity survey 2018; 4. Zeiser R et al. N Engl J Med 2017; 5. Jagasia et al. Blood 2020; 6. Naymagon S et al. Nat Rev Gastroenterol Hepatol. 2017; 7. Ohwada S et al. PLoS One 2018. GVHD: Graft Versus Host Disease Acute GVHD Overview • Impacted organs are the skin, GI tract, and liver6 • GI damage is a leading cause of mortality6 • Occurs when immune cells from the donor attack healthy recipient tissues after an allogeneic HSCT1 • 27,000 allogenic HSCTs in U.S. and Europe2,3 • 30-50% of patients can develop acute GVHD4 • Corticosteroids are 1st line SOC, however ~50% of patients become refractory5 Erosion/ulceration in patients with acute GI-GVHD7 © 2018 Ohwada et al. 28


 
Corporate Presentation 0 20 40 60 80 100 5 6 7 8 9 10 11 12 13 14 Su rv iv al (% ) Days Post-Transplant TBI Only TBI/BMT + Vehicle TBI/BMT + apraglutide Apraglutide, a Novel Regenerative Medicine Approach Compelling preclinical data support the therapeutic potential in aGVHD Source: Data on file. VectivBio. Basel, Switzerland. TBI: Total Body Irradiation; BMT: Bone Marrow Transplant; Gy: Gray (unit) Apraglutide Reduced Mortality Apraglutide Prevented GI Damage TBI (8.5 Gy)/BMT + vehicle TBI (8.5 Gy)/BMT + apraglutide TBI-BMT Model (7.0 Gy) 5/5 4/10 0/10 Preclinical Findings of Apraglutide Apraglutide received FDA Orphan Drug Designation for aGVHD in June 2021 29


 
Corporate Presentation Initial Clinical Proof-of-Concept Achieved With GLP-2 1. Norona et al. European Society for Blood and Marrow Transplantation Conference, March 2021, Abstract OS9-1 and oral presentation. Acute GVHD Phase 2 Proof of Concept Study With Apraglutide to Begin Q1 2022 Clinical Findings of GLP-2 in aGVHD1 • Methods: • N=6 • Steroid refractory aGVHD • Failed multiple therapies—five of six patients on ruxolitinib + steroids • Once daily dosing of teduglutide for 10 days • Findings: • Clinical signs of intestinal GVHD improved in all six patients with a decline in the frequency of diarrhea • Serum albumin levels increased in all patients, a parameter indicating a positive impact on patients’ nutritional status Change in Stools Per Day Change in Albumin Normal range: 3.5 – 5.5 g/dl 30


 
The CoMET platform


 
Corporate Presentation • Genetic loss of key enzymes required for cellular metabolism • Failure of energy production and accumulation of toxic metabolites • 1 in 800 births • Diagnosed in infancy • Recurrent metabolic crises • Coma and high risk of death • Progressive organ damage • Brain • Heart • Kidney • Liver • Impaired growth and severe neurodevelopmental delay 32 Inherited Metabolic Diseases Are Severe, Life-threatening Genetic Disorders Enzymatic defects result in common pathophysiology and clinical presentation Yang, L., Guo, B., Li, X. et al. Brain MRI features of methylmalonic acidemia in children: the relationship between neuropsychological scores and MRI findings. Sci Rep 10, 13099 (2020). Inherited Metabolic Diseases (IMDs) Clinical Presentation • No approved treatments • Intensive care, supportive and dietary management, liver or kidney transplant in selected cases


 
Corporate Presentation33 IMDs Fall into Groups that Share Common Affected Pathways Enzyme deficits impair substrate metabolism and coenzyme A (CoA) functionality, with widespread downstream impact OTC: ornithine transcarbamylase MCAD: medium chain Acyl-CoA dehydrogenase PK: pyruvate kinase


 
Corporate Presentation34 CoMET Platform Aims to Transform the Treatment of IMDs Modular approach to address a broad range of severe metabolic disorders a. Clin Exp Med. 2017 Aug;17(3):305-323. doi: 10.1007/s10238-016-0435-0 b. Brusilow SW, Horwich AL. Urea cycle enzymes. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds.). The Metabolic and Molecular Bases of Inherited Disease, 8th ed., New York: McGrawHill, 2001:1909–1963 c. Marsden D, Bedrosian CL, Vockley J. Impact of newborn screening on the reported incidence and clinical outcomes associated with medium- and long-chain fatty acid oxidation disorders. Genet Med. 2021 May;23(5):816-829 d. Biochem Genet. 2018 Apr;56(1-2):7-21. doi: 10.1007/s10528-017-9825-6. Epub 2017 Nov 1. Disease prevalence was estimated by multiplying annual incidence numbers by an average life expectancy of 20 years and adjusting for neonatal and infant mortality Patients in US & EU 26,000a 26,000b 16,000c 8,000d FIH Q1 2023 Discovery Preclinical Phase 1 Methyl Malonic and Propionic Acidemia Other Organic Acidemias Urea Cycle Disorders Fatty Acid Oxidation Disorders Amino Acidopathies Molecule VB-1197 VB-1200 VB-1300 VB-1400 Strong development synergies support a potentially transformative, fast-to-patient portfolio • Modular platform to deliver series of molecules that each address multiple IMDs • Common pathophysiology and clinical endpoints allow for umbrella and basket trials • Diagnosis through newborn screening and supported by existing clinical guidelines • Biochemical endpoints allow rapid biomarker-enabled drug development with small, seamless trials • Patients treated at specialist metabolic medicine units with center-of-excellence model for delivery and care


 
Corporate Presentation • Can enter cells and replenish CoA • Unstable • Rapidly cleaved by Vanin-1 to generate toxic cysteamine • Enhanced stability with systemic exposure • Labelled molecule integrates into CoA biosynthesis • Can carry conjugated cargos into cells 35 CoMET Platform Designed to Address Clusters of IMDs by Providing CoA Precursor and Disease-relevant Cargos Proprietary chemistry based on a stabilized pantetheine backbone Pantetheine Stabilized CoA precursor backbone Cargo Molecule Targeted IMDs Succinate VB-1197 Organic acidemias Undisclosed VB-1200 Urea cycle disorders Undisclosed VB-1300 Fatty acid oxidation disorders Undisclosed VB-1400 Amino acidopathies P1, P2: Proprietary protective/stabilization modifications Can carry up to 3 conjugated cargos per pantetheine backbone P1 P2 Broad Intellectual Property portfolio with projected Composition of Matter protection to at least 2040


 
Corporate Presentation36 CoMET Platform is Designed to Replenish Intracellular CoA and Missing Metabolites Stabilized pantetheine conjugated to pathway-specific cargo to restore metabolic flux


 
Corporate Presentation37 CoMET Platform Demonstrated Restoration of Intracellular Metabolism after Systemic Administration Incorporation and correction of biochemical abnormalities in animal models Source: Data on file. VectivBio. Basil, Switzerland. 1. Stabilized pantetheine was labelled with deuterium to and administered to Vitamin B5 deprived WT mice (n=4-5/treatment group) either IV or PO. Whole organs were harvested and labelled vs. endogenous CoA was measured via mass spectrometry 2. MMUT knock-in mice (Forny P et al; J Biol Chem. 2016 Sep 23; 291(39): 20563–20573) were used as a model of MMA. Mice (n=2-4/treatment group) were administered VB-1056 (1, 10, 50 mpk) for 113 days (QD) via intraperitoneal injection. Whole organs were harvested and metabolites were measured via mass spectrometry D6 labelled stabilized pantetheine in vivo1 Endogenous CoA Labelled CoA Improvement in liver metabolism in mouse model of Methyl Malonic Acidemia (MMA) with stabilized panthetheine + cargo2 Compounds incorporated Into all relevant organs Compounds correct metabolic defects Increases Levels of Functional CoA Decreases Levels of Toxic Metabolites Liver Acetyl-CoA Liver MMA Liver Heart Brain (Cerebellum)


 
Corporate Presentation38 Addressing Unmet Needs of Patients Suffering from IMDs CoMET platform has potential to deliver effective systemic therapies for many patients Desired Goal Organ Transplant Gene Therapy Vision for CoMETPlatform Broad patient eligibility Highly selected patients Specific to one genetic defect No pre-existing immunity to vector Efficacy across diseases with similar metabolic deficits Systemic benefit Transplanted organ only Targeted tissues only Systemic efficacy Safety Immunosuppression, infection risk Integration, immunogenicity Large therapeutic index Sustained efficacy Lasting effect for life of organ Duration of effect unknown Immunogenicity prevents re-use Efficacy maintained by chronic oral or subcutaneous therapy • Current management aims to manage and prevent metabolic crises through general supportive measures and strict dietary control • An ideal therapy would address intracellular metabolic defects in all tissues and for all patients


 
Corporate Presentation39 Building a Fully Integrated Global Rare Disease Company Multiple near-term catalysts Transformative CoMET platform Designed to address pre- viously intractable IMDs 4 programs in research, plans to enter the clinic in 18 months Experienced Team Apraglutide, a Compelling Phase 3 Asset SBS-IF, an underserved >$2B market opportunity Significant life- cycle potential starting with GVHD Strong track record of success 2021 2022 2023 Key Catalysts Adult SBS-IF: -Phase 3 Start: Jan -Phase 2 Start: Q2 Adult SBS-IF -Phase 3 Top-Line Results: H2 Pediatric SBS-IF -Trial Initiation: 2023 CoMET -Entry into human trials Adult SBS-IF CIC -Phase 2 Initial Results: H1 Acute GVHD -Phase 2 Start: Q1 -Interim POC read out: H2 ✓ ✓