8-K
Gain Therapeutics, Inc. (GANX)
8-K
2021-05-04
For: 2021-05-03
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Added on
April 08, 2026
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
_______________
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of report (Date of earliest event reported): May 4, 2021 (May 3, 2021)
Gain Therapeutics, Inc.
(Exact Name of the Registrant as Specified in Charter)
| Delaware | 001-40237 | 85-1726310 |
|---|---|---|
| (State or Other Jurisdiction<br><br>of Incorporation) | (Commission<br>File Number) | (IRS Employer<br><br>Identification No.) |
4800 Hampden Lane, Suite 200
Bethesda, Maryland 20814
(Address of principal executive offices) (Zip Code)
(301) 500-1556
(Registrant’s telephone number, including area code)
Not applicable
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
◻Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
◻Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
◻Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
◻Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class: | Trading symbol(s) | Name of exchange on which registered |
|---|---|---|
| Common Stock, $0.0001 par value | GANX | NASDAQ Global Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ⌧
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ⌧
**Item 8.01.**Other Events
On May 3, 2021, Gain Therapeutics, Inc. (the “Company”) issued a press release announcing new pre-clinical data from its GBA1 Parkinson's disease program. The findings were highlighted in a presentation at the XXVI International Association of Parkinsonism and Related Disorders (IAPRD) World Congress, a research conference dedicated to Parkinson’s disease and other disorders affecting muscle tone and motor control.
A copy of the press release and presentation is attached as Exhibit 99.1 and Exhibit 99.2, respectively to this Form 8-K and incorporated by reference herein.
**Item 9.01.**Financial Statements and Exhibits.
(d) Exhibits.
| | | |
|---|---|---|
| Exhibit No. | | Description |
| 99.1 | | Press release dated May 3, 2021, issued by the Company |
| 99.2 | | Presentation |
SIGNATURE
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 hereunto duly authorized.
| | GAIN THERAPEUTICS, INC. | ||
|---|---|---|---|
| | | ||
| | By: | /s/ Eric I Richman | |
| | Name: | Eric I. Richman | |
| | Title: | Chief Executive Officer |
Date: May 4, 2021
Exhibit 99.1
| Gain **** Therapeutics **** Inc.<br><br>4800 Hampden Ln, St 200<br><br>Bethesda, MD 20814<br><br>www.gaintherapeutics.com |
|---|
GAIN THERAPEUTICS PRESENTS POSITIVE IN VITRO & IN VIVO DATA ON ITS ORALLY BIOAVAILABLE **** BRAIN PENETRANT STAR COMPOUNDS FOR THE TREATMENT OF GBA1 PARKINSON’S DISEASE & **** RELATED **** α-SYNUCLEOPATHIES **** AT **** THE **** XXVI IAPRD **** WORLD **** CONGRESS
Compounds reverse the neurodegenerative process observed in a Parkinson’s disease in vivo model Compounds are novel allosteric regulators that bind, stabilize and restore activity of mutated GCase Compounds decrease both phosphorylated and aggregated α-synuclein levels in vitro and in vivo
BETHESDA, Md., May 3, 2021 – Gain Therapeutics, Inc. (NASDAQ: GANX) (“Gain”), a biotechnology company focused on redefining drug discovery by using super-computational methods to target allosteric binding sites and guide enzymes back to their proper shape, today announced new pre-clinical data from its GBA1 Parkinson’s disease program. The findings were highlighted in a presentation at the XXVI International Association of Parkinsonism and Related Disorders (IAPRD) World Congress, a research conference dedicated to Parkinson’s disease and other disorders affecting muscle tone and motor control, being held virtually May 1-4, 2021.
“These data demonstrate that our Structurally Targeted Allosteric Regulators (STARs) compounds open a new potential approach for direct treatment of GBA1 Parkinson’s disease by guiding misfolded forms of the GCase enzyme to their proper shape and restoring enzymatic activity,” said Manolo Bellotto, Ph.D., General Manager and President at Gain. “STARs bind to novel allosteric binding sites identified using our proprietary Site-Directed Enzyme Enhancement Therapy (SEE-Tx™) drug discovery platform, stabilize and restore enzymatic activity to misfolded GCase. The restoration of GCase activity results in the depletion of the toxic phosphorylated and aggregated forms of α-synuclein and a reversal of the neurodegenerative process resulting in improved locomotor activity in a Parkinson’s disease model in rats. We will continue to further explore the potential of these compounds in Parkinson’s disease and α-synucleopathies.”
Ricardo Feldman, Ph.D., Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine, stated, "Our laboratory is using human induced pluripotent stem cells (iPSC) derived from patients with GD and GBA-associated Parkinson’s disease to test the efficacy of the two lead STAR chaperones developed by Gain Therapeutics. Our early studies in iPSC-derived neurons from neuronopathic GD patients show that both STAR compounds, GT-02287 and GT-02329 are very effective in meeting target goals. These include increasing the levels of GCase protein, its transport to the lysosome, and decreasing levels of pathogenic α-synuclein. As the work in our laboratory progresses, we look forward to working with Gain’s team to further advance its GBA program.”
Eric I. Richman, Chief Executive Officer, added, “There have been many promising treatments for Parkinson’s disease that have not come to fruition. Through partnerships with the Michael J. Fox Foundation and the Silverstein Foundation for Parkinson with GBA, we identified two STAR lead candidates that have the potential to help Parkinson’s patients with GBA1 gene mutations as well as patients whose GCase protein is misfolded due to aging cellular processes. Our preclinical data demonstrates that our STAR compounds successfully target protein misfolding rather than treating symptoms of the disease, and we are honored our abstract is recognized as one of the top 10 best abstracts at IAPRD this year.”
Key findings from the presentation are highlighted below. To access the presentation please visit the Publications section of the Gain website.
Preclinical Development of Brain-Penetrant Structurally Targeted Allosteric Regulators (STARs) for the **** Treatment **** of GBA1 **** Parkinson’s **** Disease **** and Related **** α-Synucleopathies
The presented results highlight data from preclinical cell cultures and rodent models, including rotenone models of Parkinson’s disease. STARs bound misfolded forms of GCase trapped in the endoplasmic reticulum (ER) and enhanced the processing from the ER to the lysosome. This improved lysosomal GCase activity restored normal lysosomal and autophagic activity and ultimately decreased α-synuclein levels.
| ● | Two lead STAR candidates (GT-02287 and GT-02329) were identified using Gain’s proprietary SEE- |
|---|
Tx™ drug discovery platform
| ● | Both STAR compounds stabilized GCase and enhanced its enzymatic activity in human fibroblasts isolated from patients with GBA1-related Gaucher disease, which has a similar genetic profile to Parkinson’s disease |
|---|---|
| ● | Both STAR compounds were neuroprotective and lowered α-synuclein pathology in primary rat dopaminergic neurons |
| --- | --- |
| ● | When delivered orally, GT-02329 successfully penetrated the blood brain barrier and enhanced GCase activity and protein levels in the striatum of wild-type mice |
| --- | --- |
| ● | GT-02287 reduced α-synuclein accumulation in both cell culture and rat models of Parkinson’s disease |
| --- | --- |
| ● | GT-02287 improved locomotor activity in rats treated with rotenone, a model of Parkinson’s disease that reproduces certain features of the human disease |
| --- | --- |
About **** SEE-Tx™
SEE-Tx is the first technology platform exclusively designed to use the 3D structure of proteins to systematically identify allosteric binding sites never described previously and predict their druggability. Powered by supercomputers, its novel algorithm orchestrates molecular modeling at a speed and efficiency that has the potential to redefine drug discovery.
About **** Gain Therapeutics, **** Inc.
Gain Therapeutics, Inc. is redefining drug discovery with its SEE-Tx™ target identification platform. By identifying and optimizing allosteric binding sites that have never before been targeted, Gain is unlocking new treatment options for difficult-to-treat disorders characterized by protein misfolding. Gain was established in 2017 with the support of its founders and institutional investors. It has been awarded funding support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The Silverstein Foundation for Parkinson’s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse. In July 2020, Gain Therapeutics, Inc. completed a share exchange with Gain Therapeutics, SA, a Swiss corporation, whereby GT Gain Therapeutics SA became a wholly owned subsidiary of Gain Therapeutics, Inc.
Forward-Looking **** Statements
Any statements in this release that are not historical facts may be considered to be “forward-looking statements.” Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties which may cause results to differ materially and adversely from the statements contained herein. Such statements include, but are not limited to, statements regarding the market opportunity for Gain’s product candidates; and the business strategies and development plans of Gain. Some of the potential risks and uncertainties that could cause actual results to differ from those expected include Gain’s ability to: make commercially available its products and technologies in a timely manner or at all; enter into other strategic alliances, including arrangements for the development and distribution of its products; obtain intellectual property protection for its assets; accurately estimate its expenses and cash burn and raise additional funds when necessary. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made. Except as required by law, Gain does not undertake any obligation to update any forward-looking statements to reflect new information, events or circumstances after the date they are made, or to reflect the occurrence of unanticipated events.
Gain **** Therapeutics **** Investor **** Contact:
Daniel Ferry LifeSci Advisors
+1 617-430-7576
daniel@lifesciadvisors.com
Gain **** Therapeutics **** Media **** Contact:
Madeline Joanis
LifeSci Communications
+1 646-751-4366
mjoanis@lifescicomms.com
Exhibit 99.2
| © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Leading the Discovery of<br>Allosteric Binding Sites to<br>Create New Medicines |
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| Page 2 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Forward-Looking Statements<br>Certain statements set forth in this presentation contain forward-looking statements that reflect the Company’s plans, beliefs, expectations and current views with respect to, among other things, future events and financial performance (collectively referred<br>to herein as “forward-looking statements”). Forward-looking statements can be identified by the fact that they do not relate strictly to historical or current facts and are often characterized by the use of words such as “believe,” “can,” “could,” “potential,”<br>“plan,” “predict,” “goals,” “seek,” “should,” “may,” “may have,” “would,” “estimate,” “continue,” “anticipate,” “intend,” “expect” or by discussions of strategy, plans or intentions. Such forward-looking statements involve known and unknown risks,<br>uncertainties, assumptions and other important factors that could cause our actual results, performance or achievements or industry results to differ materially from historical results or any future results, performance or achievements expressed, suggested<br>or implied by such forward-looking statements.<br>These include, but are not limited to, statements about the Company’s ability to develop, obtain regulatory approval for and commercialize its product candidates; the timing of future IND submissions, initiation of preclinical studies and clinical trials, and<br>timing of expected clinical results for our product candidates; the Company’s success in early preclinical studies, which may not be indicative of results obtained in later studies or clinical trials; the outbreak of the novel strain of coronavirus disease, COVID-<br>19, which could adversely impact our business, including our preclinical studies and any future clinical trials; the potential benefits of our product candidates; the Company’s ability to obtain regulatory approval to commercialize our existing or any future<br>product candidates; the Company’s ability to identify patients with the diseases treated by our product candidates, and to enroll patients in clinical trials; the success of our efforts to expand our pipeline of product candidates and develop marketable<br>products through the use of our SEE-Tx platform; the Company’s expectations regarding collaborations and other agreements with third parties and their potential benefits; the Company’s ability to obtain, maintain and protect our intellectual property; the<br>Company’s reliance upon intellectual property licensed from third parties, including the license to use our SEE-Tx platform; the Company’s ability to identify, recruit and retain key personnel; the Company’s expected use of net proceeds from this offering<br>and the sufficiency of such net proceeds, together with the Company’s cash and cash equivalents, to fund its operations; the Company’s financial performance; developments or projections relating to the Company’s competitors or industry; the impact of<br>laws and regulations; the Company’s expectations regarding the time during which it will be an emerging growth company under the JOBS Act; and other factors and assumptions described in the Company’s public filings.<br>These statements are based on the Company’s historical performance and on its current plans, estimates and projections in light of information currently available to the Company, and therefore, you should not place undue reliance on them. The inclusion<br>of forward-looking information should not be regarded as a representation by the Company or any other person that the future plans, estimates or expectations contemplated by us will be achieved. Forward-looking statements made in<br>this presentation speak only as of the date of this presentation, and the Company undertakes no obligation to update them in light of new information or future events, except as required by law.<br>You should carefully consider the above factors, as well as the factors discussed elsewhere in this presentation and our public filings, before deciding to invest in our common stock. The factors identified above should not be construed as an exhaustive list<br>of factors that could affect the Company’s future results, and should be read in conjunction with the other cautionary statements that are included in this presentation and our public filings. New risks and uncertainties arise from time to time, and it is<br>impossible for the Company to predict those events or how they may affect the Company. If any of these trends, risks or uncertainties actually occurs or continues, the Company’s business, revenue and financial results could be harmed, the trading prices<br>of its securities could decline and you could lose all or part of your investment. All forward-looking statements attributable to the Company or persons acting on its behalf are expressly qualified in their entirety by this cautionary statement.<br>Trademarks, Service Marks, and Trade Names<br>This presentation includes our trademarks, and trade names, including but not limited to Site-Directed Enzyme Enhancement Therapy, or SEE-Tx, which are protected under applicable intellectual property laws. This presentation also may contain<br>trademarks, service marks, trade names, and copyrights of other companies, which are the property of their respective owners. Solely for convenience, the trademarks, service marks, trade names, and copyrights referred to in this presentation are listed<br>without the TM, SM, ©, and ® symbols, but we will assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensors, if any, to these trademarks, service marks, trade names, and copyrights.<br>Industry Information<br>Market data and industry information used throughout this presentation are based on management’s knowledge of the industry and the good faith estimates of management. We also relied, to the extent available, upon management’s review of independent<br>industry surveys and publications and other publicly available information prepared by a number of third party sources. All of the market data and industry information used in this presentation involves a number of assumptions and limitations, and you are<br>cautioned not to give undue weight to such estimates. Although we believe that these sources are reliable, we cannot guarantee the accuracy or completeness of this information, and we have not independently verified this information. While we believe<br>the estimated market position, market opportunity and market size information included in this presentation are generally reliable, such information, which is derived in part from management’s estimates and beliefs, is inherently uncertain and imprecise. No<br>representations or warranties are made by the Company or any of its affiliates as to the accuracy of any such statements or projections. Projections, assumptions and estimates of our future performance and the future performance of the industry in which<br>we operate are necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including those described above. These and other factors could cause results to differ materially from those expressed in our estimates and beliefs and in<br>the estimates prepared by independent parties.<br>Forward-Looking Statement |
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| Page 3 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Platform Technology<br>Robust Pipeline<br>Upcoming Milestones<br>• Proprietary and patented SEE-Tx platform identifies allosteric (non-catalytic) binding sites in proteins and<br>enzymes that can regulate proper protein folding to restore functional activity<br>• Convergence of Computational Biology and Supercomputing<br>Therapeutic Focus<br>• Demonstrated targeted engagement<br>• Strong intellectual property estate-5 new NCE families patented<br>Global Partnerships • Strong relations with academic centers, key patient associations, and development partners<br>• Partnership established with Sumitomo and Zentalis with potential to establish additional partnerships<br>Team • Seasoned and experienced management team, board of directors and scientific advisors<br>• Near term milestones: several development candidates currently completing animal POC<br>• IND enabling studies starting 2021<br>• Addressing Protein Misfolding by identifying and targeting novel previously undruggable allosteric binding sites<br>• Initial focus on lysosomal storage and CNS diseases -- large & growing markets with unmet medical need<br>Executive Summary |
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| Page 4 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Gain leverages its proprietary platform technology to engineer novel therapeutics targeting<br>conditions with significant unmet needs<br>SEE-Tx Discovery Platform<br>• Proprietary supercomputer-driven drug discovery platform<br>• Identifies novel allosteric binding sites on misfolded proteins<br>• Enables targeting of novel allosteric binding sites and generation of<br>proprietary molecules efficiently and quickly<br>1<br>Diversified Pipeline of Drug Candidates<br>targeting multi-billion $ markets<br>• Pipeline candidates translated from SEE-Tx platform to preclinical<br>development<br>• Primarily targeting lysosomal storage disorders and generic<br>neurodegenerative disorder, including:<br>• Morquio B/ GM1 Gangliosidosis<br>• Gaucher Disease<br>• Parkinson’s Disease<br>• Opportunity to expand into other indications addressing protein<br>misfolding<br>2<br>Gain Therapeutics’ Dual-pronged Approach to Value Generation<br>Discovery Pre-Clinical Clinical<br>Gene Disease in vitro in vivo Lead OP IND-<br>Enabling Phase 1 Phase 2 Phase 3<br>GLB1 gene Morquio B /<br>GM1 Gangliosidosis<br>GBA1 gene Gaucher Disease<br>GBA1 gene Parkinson’s Disease<br>IDUA gene Mucopolysaccharidosis<br>type 1<br>GALC gene Krabbe Disease<br>R&D collaboration with Sumitomo on an undisclosed target<br>Multi-target discovery & development collaboration with Zentalis<br>Demyelinating Disease<br>Oncology |
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| Page 5 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Lysosomal Storage Disorders<br>LSDs represent significant<br>markets with high unmet<br>needs, especially in<br>neurological conditions<br>Neurodegeneration<br>A multi billion-dollar market<br>with high unmet needs in a<br>growing patient population<br>SOC Challenges: Inability to access hard to reach tissues<br>Future Applications<br>Oncology, Mitochondrial<br>Diseases, Immunology,<br>Metabolic Disorders<br>Key Markets: Broad Platform Applicability |
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| Page 6 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Binding allosteric sites has the potential to provide superior regulation of misfolded enzymes implicated in diseases.<br>Misfolded enzymes cannot properly catalyze their intended substrates, leading to toxic substrate accumulation.<br>Structurally Targeted<br>Allosteric Regulators<br>(STARs)<br>Corrected Folding of Enzymes to Restore Functional Activity |
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| Page 7 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>IDENTIFY<br>Using the 3D structure of proteins<br>and supercomputing technology,<br>SEE-Tx identifies novel druggable<br>binding hotspots<br>SCREEN & SELECT<br>Utilizing proprietary supercomputer<br>driven screening methodology,<br>SEE-Tx filters up to 10 million<br>compounds to select a pool of<br>candidates that may bind to the<br>novel druggable hotspots<br>OPTIMIZE<br>Gain optimizes this pool of small<br>molecules to identify and develop<br>proprietary STARs that stabilize<br>misfolded proteins and to restore<br>their biological activity<br>DEVELOPMENT CANDIDATE<br>Gain has patented methodology & algorithm (WIPO/PCT WO 2013/092922 A2).<br>DIFFERENTIATED and PATENTED highly-specific, efficient and cost-effective drug discovery approach<br>DEFECTIVE PROTEIN<br>Stabilizes protein enzyme, restores enzyme function, reduces substrate buildup, crosses the blood brain<br>barrier, and penetrates other hard to reach tissues such as bone and cartilage.<br>Caused by genetic mutation, ageing, and disease. Results in loss of protein function and toxic substrate buildup.<br>SEE-Tx™ Discovery Platform |
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| Page 8 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Allosteric Binding Site<br>• Non-competitive with the natural<br>substrate<br>• High specificity for the targeted<br>enzyme<br>• Superior drug-like properties<br>• Offer a broader therapeutic window<br>Active Binding Site<br>• Site where enzyme binds<br>substrate to catalyze reaction<br>• Traditional drugs bind to active<br>sites<br>• Competes with active substrate -<br>decreases efficacy<br>• May lead to selectivity issues<br>Active binding site Allosteric binding site<br>Binding allosteric sites has the potential to provide superior regulation of misfolded enzymes implicated in diseases.<br>Advantages of Drugging Allosteric Binding Sites |
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| Page 9 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Criteria for Selection of STARs<br>1 2 5 3<br>• STARs: Novel small molecule compounds selected to bind to allosteric<br>sites and restore protein function, cross blood-brain barrier and access<br>bone, cartilage and other hard to reach tissues<br>• Easily scalable small molecules with potential oral bioavailability<br>• Improved pharmacokinetic (PK) profile with better safety profile and<br>therapeutic window<br>• No interaction with the target enzyme’s active site and ability to<br>stimulate wild-type enzyme activity<br>4<br>Previously<br>unidentified<br>allosteric site<br>Stabilizes misfolded protein<br>with potential to restore<br>biological activity<br>Crosses the blood<br>brain barrier after oral<br>administration<br>Reduces toxic<br>substrate<br>Highly<br>specific<br>SEE-Tx™ Platform Produces Novel STARs |
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| Page 10 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Discovery Pre-Clinical Clinical<br>Gene Disease in vitro in vivo Lead OP IND-<br>Enabling Phase 1 Phase 2 Phase 3<br>GLB1 gene Morquio B /<br>GM1 Gangliosidosis<br>GBA1 gene Gaucher Disease<br>GBA1 gene Parkinson’s Disease<br>IDUA gene Mucopolysaccharidosis<br>type 1<br>GALC gene Krabbe Disease<br>Diversified Pipeline Targeting Multi-Billion Dollar Markets<br>R&D collaboration with Sumitomo Dainippon Pharma on an undisclosed target<br>Multi-target discovery & development collaboration with Zentalis Pharmaceuticals<br>Demyelinating Disease<br>Oncology |
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| © 2021 - GAIN THERAPEUTICS Non-Confidential Presentation<br>GM1 Gangliosidosis/Morquio B<br>Beta-galactosidase (GLB1)<br>The Programs |
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| Page 12 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Deficiency of acid β -galactosidase causes GM1 gangliosidosis and Morquio disease type B (MPS IVB)<br>Currently, no effective medical treatment for GLB1-related disorders.<br>Symptomatic treatment for some neurologic sequelae but does not alter the clinical course.<br>GLB1-related Disorders: GM1 and Morquio B<br>GM1 Gangliosidosis<br>• Indidence worldwide (1:100,000-200,000 newborns).1<br>• β-galactosidase is responsible for breaking down GM1-ganglioside, abundance of<br>ganglioside results in neurodegeneration and severe neurological conditions.<br>• Symptoms include developmental regression, skeletal abnormalities, loss of vision,<br>and seizures.<br>Morquio B<br>• Prevalence worldwide (1:250,000-1,000,000).2<br>• It is caused by genetic mutation of GLB1 gene that eliminates activity of β-<br>galactosidase leading to accumulation of keratan sulphate in organs and tissues.<br>• Symptoms include loss of nerve function, abnormal bone and spine development,<br>and hearing loss.<br>1Lysogene<br>2Elsevier doi:10.1016/j.ymgmr.2018.06.006<br>Life-long chronic<br>treatment targeting<br>over 7000 patients<br>Peak sales: > $1 billion |
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| Page 13 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GM1/Morquio B Program Summary: Lead Candidate GT-00513<br>Mechanism of Action<br>• Dose-dependent binding of β-gal<br>• Non-competitive activity<br>• Support proper folding and protein maturation<br>Drug Properties<br>• High oral bioavailability<br>• Penetrates well into Brain (CNS) and<br>bone (skeletal)<br>• Half-life suitable for once daily use<br>• Well-tolerated in multiple dose (sub-<br>chronic) toxicity studies<br>Small (400 Da) molecule with good drug-like properties<br>PCT application published July 2018<br>National phases 2019<br>in vitro Target Engagement<br>• Enzyme stabilization and enzymatic<br>enhancement in fibroblasts<br>• Clearance of toxic substrate in fibroblasts<br>Intellectual Property (IP) |
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| Page 14 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>HEK293 were transfected with either GLB1 WT, GLB1 I51T, GLB1 R201C and GLB1 W273L with HaloTag. 30 hours later, compounds (25 µM) and a<br>fluorescent Halo ligand that covalently binds to a pocket in the tag were added for 17 hours. Once the protein reaches the lysosome, the tag is<br>cleaved off. The 31 KDa tag is resistant to lysosomal hydrolases and it can be detected as a fluorescent fragment that corresponds to the protein that<br>reached the lysosomes. Full length protein and lysosomal fragment are measured by western blot.<br>GT-00513: Increases the Delivery of β-Gal to the Lysosome<br>GLB1 WT GLB1 I51T GLB1 W273L<br>Control<br>GT-00513<br>Bafilom<br>ycin A1<br>0<br>100<br>200<br>300<br>H<br>T<br><br>f<br>r<br>a<br>g<br>m<br>e<br>n<br>t<br><br>(<br>%<br><br>t<br>o<br><br>D<br>M<br>S<br>O<br>)<br>Control<br>GT-00513<br>Bafilom<br>ycin A1<br>0<br>100<br>200<br>300<br>H<br>T<br><br>f<br>r<br>a<br>g<br>m<br>e<br>n<br>t<br><br>(<br>%<br><br>t<br>o<br><br>D<br>M<br>S<br>O<br>)<br>Control<br>GT-00513<br>Bafilom<br>ycin A1<br>0<br>200<br>400<br>600<br>800<br>1000<br>H<br>T<br><br>f<br>r<br>a<br>g<br>m<br>e<br>n<br>t<br><br>(<br>%<br><br>t<br>o<br><br>D<br>M<br>S<br>O<br>) |
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| Page 15 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GT-00513: Reduces GM1 Ganglioside Accumulation<br>GM1 gangliosidosis canine fibroblasts (p.R60H/p.R60H; equivalent to<br>R59H mutation in humans) were loaded with GM1 ganglioside for 2<br>days followed by culture in the presence of GT-00413 at 25 µM for 4<br>subsequent days. The cells were fixed, permeabilized and stained to<br>detect GM1ganglioside.Nuclei were counterstained with DAPI.<br>0.00<br>0.01<br>0.02<br>0.03<br>0.04<br>GM1 ganglioside<br>G<br>M<br>1<br><br>g<br>a<br>n<br>g<br>l<br>i<br>o<br>s<br>i<br>d<br>e<br><br>(<br>n<br>g<br>/<br>µ<br>g<br><br>)<br>Untreated<br>GT-00513 (25 µM)<br>GT-00413 (25 µM)<br>p.R60H/p.R60H canine fibroblasts (Coriell GM11473) were treated with 25<br>µM of GT-00513 in triplicates. Cells were harvested at day 4 and samples<br>were analysed for GM1 ganglioside quantification using MS/MS. Data is<br>expressed as mean ± SD (n=1, preliminary results).<br>GLB1 fibroblasts<br>accumulate GM1<br>ganglioside<br>STARS are effective in<br>reducing substrate<br>accumulation<br>GM1 ganglioside |
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| Page 16 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GT-00513: Demonstrates High Oral Bioavailability<br>Plasma pharmacokinetics of GT-00513.HCl following a single intravenous and oral administration to male C57BL/6 mice. n=3 and data are expressed as mean ± SD.<br>GT-00513.HCl salt oral bioavailability, F = 76%.<br>GT-00513, IV, 2 mg/kg, Brain<br>GT-00513, PO, 10 mg/kg, Brain<br>GT-00513, IV, 2 mg/kg, Plasma<br>GT-00513, PO, 10 mg/kg, Plasma<br>Brain-to-plasma ratio ranged 0.42-0.72<br>Route<br>Dose<br>(mg/<br>kg)<br>Test System Tmax<br>(hr)<br>aCo/Cmax<br>(ng/mL)<br>AUClast<br>(hr*ng/mL)<br>AUCinf<br>(hr*ng/mL)<br>T1/2<br>(hr)<br>CL<br>(mL/min/kg)<br>Vss<br>(L/kg)<br>%<br>Fb<br>GT-00513 IV 2 male C57BL/6 mice - 1181.29 1195.16 1314.68 4.39 25.35 6.12 -<br>GT-00513 PO 10 male C57BL/6 mice 0.5 1140.21 4548.73 4711.51 76<br>Plasma exposure Brain exposure |
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| Page 17 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GT-00513: Penetrates well into both Brain and Bone<br>0<br>2000<br>4000<br>6000<br>8000<br>Time (h)<br>C<br>o<br>n<br>c<br>..<br><br><br>(<br>n<br>g<br>/<br>m<br>L<br><br>o<br>r<br><br>n<br>g<br>/<br>g<br>)<br>Plasma (90 mg/kg,po)<br>Brain (90 mg/kg,po)<br>Left femur (90 mg/kg,po)<br>Plasma (180 mg/kg,po)<br>Brain (180 mg/kg,po)<br>Left femur (180 mg/kg,po)<br>1 4 8<br>Plasma, brain and left femur concentration-time data of GT-0513 in male C57BL/6 mice on day 7 |
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| Page 18 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GM1/Morquio B Program Status and Next Steps<br>Lead Candidate GT-0513<br>• Demonstration of mechanism of action<br>indicative of specific binding and<br>bypassing protein quality control of<br>protein misfolding<br>• Demonstration of in vitro of target<br>engagement as measured by β-<br>galactosidase enhancement and toxic<br>GM1 gangliosides depletion<br>• Orally bioavailable, brain and bone<br>penetrant<br>Upcoming milestones<br>• In vivo POCs (Morquio B + GM1) (2021)<br>• CD Characterization/Synthesis scale-up<br>(2021)<br>• IND/CTA-enabling studies (2021-2022)<br>• Phase 1/2: SAD/MAD (safety/PK) in pediatric<br>population (2023-2024) |
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| © 2021 - GAIN THERAPEUTICS Non-Confidential Presentation<br>Gaucher/Parkinson’s Disease<br>Beta-glucosidase (GBA)<br>The Programs |
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| Page 20 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GBA1 Related Disease: Gaucher and Parkinson’s Disease<br>Mutations in the GBA1 gene are responsible for build-up of glucosylceramide in Gaucher disease and is associated with α-<br>synuclein accumulation in Parkinson’s.<br>Gaucher Disease<br>• There are approximately 1,000-2,000 patients with Neuronopathic (Type 2 and 3) Gaucher’s<br>Disease in the US and Europe. (1:100,000 newborns).1<br>• Mutations in the GBA gene cause deficiency in glucocerebrosidase enzyme, resulting in<br>glucosylceramide build up in the liver, spleen, bone marrow and nervous system<br>• Characterized by severe neurological symptoms such as abnormal eye movements, seizures, and<br>brain damage.<br>Parkinson’s Disease<br>• Parkinson’s Disease affects 10 million people worldwide. Approximately 500,000 with<br>Parkinson's have a GBA1 mutation. (5% of all Parkinson's Patients) 2<br>• GBA mutations result in early onset, faster progression, and various non-motor symptoms due<br>to accumulation of α-synuclein.<br>• Symptoms include uncontrollable shaking/tremors, slowed movement, and stiffness in limbs.<br>Currently, no effective medical treatment for GBA1-related disorders.<br>Symptomatic treatment for some neurologic sequelae but does not alter the clinical course.<br>1Lysogene<br>2Exon Publications<br>Life-long chronic<br>treatment targeting over<br>7000 patients<br>Peak sales: > $900 million<br>Disease modifying<br>treatment targeting over<br>2.4m patients<br>Peak sales: > $5 billion |
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| Page 21 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GBA Program: Lead Candidates GT-02287 and GT-02329<br>Mechanism of Action<br>• Dose-dependent and non-competitive binding to<br>GCase<br>• Stabilization of target enzyme, support proper folding<br>and protein maturation<br>in vivo Target Engagement<br>• In vivo GCase enzyme enhancement<br>• Synuclein depletion, neuroprotection etc.<br>• In vivo locomotor improvement in<br>rotenone animal model<br>GT02287 and GT02329 are small molecules of 350-450 Da with good drug-like properties<br>PCT application published July 2018<br>National phases 2019, Add. PCT files Nov. 2021 Intellectual Property (IP)<br>in vitro Target Engagement<br>• Enzymatic enhancement in patient cells in the sub-micromolar<br>range<br>• Enzymatic enhancement in dopaminergic neurons<br>• Neuroprotection in a cellular model<br>• Clearance of phosphorylated and aggregated synuclein in<br>neuronal cell models<br>• Clearance of glucosylceramide and glucosylsphingosine in cells<br>Drug Properties<br>• Oral bioavailability<br>• Brain penetration<br>• Well tolerated in acute and<br>sub-chronic toxicity studies<br>• Non cytotoxic & non<br>mutagenic |
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| Page 22 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GT compounds enhance GCase activity in a dose-dependent manner<br>WT fibroblasts<br>STARs Enhance GCase at Sub-Micromolar Concentrations<br>Gaucher-patient fibroblasts were treated with compounds at different concentrations (0.2 – 25 µM) in sextuplicate. After a 4-day<br>treatment, GCase activity was assessed using the 4-MU-β-D-glucopyranoside substrate. Fold increase compared with non-<br>treated cells was calculated.<br>Log Conc. (M)<br>%<br><br>E<br>n<br>h<br>a<br>n<br>c<br>e<br>m<br>e<br>n<br>t<br><br>v<br>s<br><br>N<br>T<br>-6.9 -6.6 -6.3 -6.0 -5.7 -5.4 -5.1 -4.8 -4.5<br>0<br>50<br>100<br>150<br>200<br>GT-02287<br>GT-02329<br>p.L444P/p.L444P fibroblasts<br>(Gaucher type II)<br>Log Conc. (M)<br>%<br><br>E<br>n<br>h<br>a<br>n<br>c<br>e<br>m<br>e<br>n<br>t<br><br>v<br>s<br><br>N<br>T<br>-6.9 -6.6 -6.3 -6.0 -5.7 -5.4 -5.1 -4.8<br>0<br>50<br>100<br>150<br>200<br>GT-02287<br>GT-02329<br>Log Conc. (M)<br>%<br><br>E<br>n<br>h<br>a<br>n<br>c<br>e<br>m<br>e<br>n<br>t<br><br>v<br>s<br><br>N<br>T<br>-5.8 -5.5 -5.2 -4.9 -4.6 -4.3<br>0<br>50<br>100<br>150 GT-02329<br>GT-02287<br>p.N370S/ins fibroblasts<br>(Gaucher type I) |
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| Page 23 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>GT compounds enhance GCase activity in wild-type and patient-derived Gaucher fibroblasts<br>Gaucher patient-fibroblasts, WT fibroblasts were treated with GT compounds, isofagomine at 12.5 µM. After 4-day treatment, GCase activity was assessed using 4-MU-β-D-<br>glucopyranoside substrate. The assay reaction is started by the addition of 28 µL of 5 mM of 4-MU-beta-D-glucopyranoside in 0.1 M acetate buffer (pH 4) to each well.<br>Plates are incubated at 37ºC for 1h and the reaction is stopped by the addition of 200 µL of glycine buffer (pH 10.7) to each well. Liberated 4-methylumbelliferone is<br>measured (excitation 340 nm, emission 460 nm). Fold increase compared with non-treated cells was calculated.<br>STARs Enhance Enzyme Activity in Patient Fibroblasts<br>GT-02287<br>1.00<br>1.25<br>1.50<br>1.75<br>2.00<br>2.25<br>2.50<br>p.N188S/p.S107L<br>p.L444P/p.R496C<br>p.L444P/p.F213I<br>p.L444P/p.L444P<br>p.N370S/p.V394L<br>p.N370S/ins<br>p.L444P/p.L444P<br>WT<br>Fold enhancement<br>Gaucher<br>type III<br>fibroblasts<br>(nGD)<br>1.00<br>1.25<br>1.50<br>1.75<br>2.00<br>2.25<br>2.50<br>p.N188S/p.S107L<br>p.L444P/p.R496C<br>p.L444P/p.F213I<br>p.L444P/p.L444P<br>p.N370S/p.V394L<br>p.N370S/ins<br>p.L444P/p.L444P<br>WT<br>Fold enhancement<br>GT-02329 |
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| Page 24 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Dopaminergic neurons BE(2)-M17 carrying either wild-type or mutant N370S, L444P or D409V GBA1 mutations were treated for 4 days with 25 µM of GT-compounds. GCase<br>activity was measured with 4-methylumbelliferyl-β-D-glucopyranoside. For the 10 days incubation experiment, media exchange with compound is performed after 3 days, then<br>after 4 days and finally cells are harvested after 3 additional days.<br>In a Neuronal Cellular Model STARs increase GCase activity of wild-type as well as GCase carrying the<br>most prevalent mutations (top) and Reduce Glucosylsphingosine Levels (bottom)<br>Dopaminergic neurons BE(2)-M17 carrying either wild-type or mutant N370S, L444P or D409V GBA1 mutations were treated for 10 days with 25 µM of GT-02287 or GT-02329<br>compounds. Media exchange with compound was performed after 3 days, then after 4 days and finally cells are harvested after 3 additional days. GlcSph (Lyso-Gb1) levels<br>were quantified by LC-MS/MS.<br>WT<br>0<br>1<br>2<br>3<br>F<br>o<br>l<br>d<br><br>e<br>n<br>h<br>a<br>n<br>c<br>e<br>m<br>e<br>n<br>t<br>(<br>G<br>C<br>a<br>s<br>e<br><br>a<br>c<br>t<br>i<br>v<br>i<br>t<br>y<br>)<br>N370S<br>0<br>1<br>2<br>3<br>F<br>o<br>l<br>d<br><br>e<br>n<br>h<br>a<br>n<br>c<br>e<br>m<br>e<br>n<br>t<br>(<br>G<br>C<br>a<br>s<br>e<br><br>a<br>c<br>t<br>i<br>v<br>i<br>t<br>y<br>)<br>L444P<br>0<br>1<br>2<br>3<br>F<br>o<br>l<br>d<br><br>e<br>n<br>h<br>a<br>n<br>c<br>e<br>m<br>e<br>n<br>t<br>(<br>G<br>C<br>a<br>s<br>e<br><br>a<br>c<br>t<br>i<br>v<br>i<br>t<br>y<br>)<br>WT<br>0<br>50<br>100<br>L<br>y<br>s<br>o<br>-<br>G<br>b<br>1<br>(<br>%<br><br>t<br>o<br><br>u<br>n<br>t<br>r<br>e<br>a<br>t<br>e<br>d<br>)<br>L444P<br>0<br>50<br>100<br>L<br>y<br>s<br>o<br>-<br>G<br>b<br>1<br>(<br>%<br><br>t<br>o<br><br>u<br>n<br>t<br>r<br>e<br>a<br>t<br>e<br>d<br>)<br>N370S<br>0<br>50<br>100<br>L<br>y<br>s<br>o<br>-<br>G<br>b<br>1<br>(<br>%<br><br>t<br>o<br><br>u<br>n<br>t<br>r<br>e<br>a<br>t<br>e<br>d<br>)<br>D409V<br>0<br>1<br>2<br>3<br>F<br>o<br>l<br>d<br><br>e<br>n<br>h<br>a<br>n<br>c<br>e<br>m<br>e<br>n<br>t<br>(<br>G<br>C<br>a<br>s<br>e<br><br>a<br>c<br>t<br>i<br>v<br>i<br>t<br>y<br>) GT-02287<br>Untreated<br>GT-02329<br>D409V<br>0<br>1<br>2<br>3<br>F<br>o<br>l<br>d<br><br>e<br>n<br>h<br>a<br>n<br>c<br>e<br>m<br>e<br>n<br>t<br>(<br>G<br>C<br>a<br>s<br>e<br><br>a<br>c<br>t<br>i<br>v<br>i<br>t<br>y<br>) GT-02287<br>Untreated<br>GT-02329 |
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| Page 25 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>STARs Decrease α-Synuclein Levels in a Neuronal Cell Model<br>Decrease in syn levels. Phosphorylated–synuclein (S129) detected by immunofluorescence in 3 differentiated neuronal cell lines (WT, N370S and L444P) treated for 15 days with 25 µM<br>of the selected GT-1 chaperone. Between 30 and 40 individual cells for each condition were quantified (mean intensity in cytosol area). Results are presented as mean ± S.E.M.value.<br>Hoechst Phosphorylated-α-synuclein (S129)<br>N370S L444P<br>Vehicle<br>STARs |
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| Page 26 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Statistical analysis was performed using GraphPad Prism software version 5.0. and used One way ANOVA followed by Dunnett’s post-hoc test; All the values<br>are expressed as Mean ± SEM. *P<0.05 Vs Vehicle control GT-02329 was administered orally, twice a day, for 12 days. Samples were collected 1 hr after the<br>last administration. N=10 per group<br>Striatum<br>0<br>2<br>4<br>6<br>8<br>29.74%<br>Vehicle Control (10 mL/kg, p.o., BID)<br>GT-02329 (60 mg/kg, p.o., BID)<br>GT-02329 (90 mg/kg, p.o., BID)<br>30.58%<br>GCase Activity (nmols/mg protein/hr)<br>STARs Enhance WT GCase Activity in Plasma and Striatum |
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| Page 27 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>STARs Show Depletion of alpha-Synuclein, Increase in Tyrosine Hydroxylase and<br>Improvement in Locomotor Activity and Markers in a Rotenone Rat Model<br>Data is shown as Mean ± S.E.M.(n=10). Unpaired T test.<br>Significant difference as compared to Rotenone control *P<br>< 0.05 P<0.05 Vs Vehicle control. GT-02287 was<br>administered orally, twice a day, for 7 days.<br>Data is shown as Mean ± S.E.M.(n=10), Ove-way ANOVA<br>followed by Dunnett’s Multiple Comparison test,<br>*Significant difference as compared to Rotenone<br>***P<0.0001, Vs Vehicle control. GT-02287 was<br>administered orally, twice a day, for 7 days.<br>Data is shown as Mean ± S.E.M.(n=10), Ove-way ANOVA<br>followed by Dunnett’s Multiple Comparison test,<br>*Significant difference as compared to Rotenone<br>***P<0.0001, Vs Vehicle control. GT-02287 was<br>administered orally, twice a day, for 7 days<br>Improvement in Locomotor Activity alpha-Synuclein Depletion Dopaminergic Neurons Activity Improvement |
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| Page 28 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Gaucher and Parkinson’s Disease Program Summary<br>Lead Candidates<br>• Demonstration of mechanism of action indicative<br>of specific binding and bypassing protein quality<br>control of protein misfolding<br>• Demonstration of in vitro of target engagement<br>as measured by enzyme enhancement and toxic<br>substrates depletion<br>• Demonstration of in vivo target engagement as<br>measured of GCase enhancement, toxic α-<br>synuclein, glucosylceramide and<br>glucosylsphingosine depletion, increase od<br>dopaminergic neurons viability marker, decrease<br>of locomotor deficits<br>• Orally bioavailable, brain penetrant<br>Upcoming milestones<br>• Gaucher and Parkinson animal models POC<br>(2021)<br>• CD Characterization/Synthesis scale-up (2021)<br>• IND/CTA-enabling studies (2021-2022)<br>• GD: Phase 1/2: SAD/MAD (safety/PK) in<br>pediatric population (2023-2024)<br>• PD: Phase 1: SAD/MAD (safety/PK) 60 healthy<br>volunteers (2022 -2023) |
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| © 2021 - GAIN THERAPEUTICS Non-Confidential Presentation<br>Mucopolysaccharidosis Type I (MPS I)<br>alpha-L-iduronidase (IDUA)<br>Program to bring forward |
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| Page 30 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Current treatments are enzyme replacement therapy and stem cell transplant.<br>Significant unmet medical are related to hard-to-treat tissues such bone and cartilage<br>Mucopolysaccharidosis type I (MPS I) is an autosomal recessive inherited disorder of metabolism where large sugar molecules<br>glycosaminoglycans (GAGs) cannot be adequately degraded<br>IDUA Related Disorders: Mucopolysaccharidosis Type I (MPS I)<br>Mucopolysaccharidosis Type I<br>• Annually, there are approximately 1,400 patients with MPS I worldwide (1:100,000).1<br>• Mutations in the IDUA gene cause deficiency in the enzyme alpha-L-iduronidase, resulting in GAG<br>build up within cells and lysosomes<br>• Symptoms include enlarged tonsils and/or adenoids, coarse facial features, abnormal curvature of the<br>spine enlargement of the liver and spleen, compression of the spinal cord, and progressive<br>neurological decline<br>• Disease progression poses a significant burden to patients and majority of progressive symptoms<br>occur in hard-to-treat tissues such as bone and cartilage – areas Gain’s STAR molecules can<br>penetrate.<br>1US National Library of Medicine |
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| Page 31 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Status<br>Animal PoC<br>Druggable allosteric site identified<br>T est compound displays:<br>- Stabilization and prevention of enzyme denaturation in<br>physiological conditions<br>- Enzymatic enhancement of ERT<br>- In vivo stabilization of recombinant IDUA (laronidase)<br>including prolonged exposure in bone tissue and<br>cartilage. Allows laronidase (Biomarin/Sanofi’s drug) to<br>reach good exposure levels in bone tissue and cartilage<br>(makes it effective in those tissues)<br>Intellectual Property (IP)<br>- PCT Patent filed (Feb. 2021)<br>Next Steps<br>Industry Collaboration<br>- in vitro efficacy study (2021)<br>MPS-I Program Summary<br>2h (G1)<br>2h (G3)<br>2h (G4)<br>8h (G1)<br>8h (G3)<br>8h (G4)<br>10h (G1)<br>10h (G3)<br>10h (G4)<br>0<br>1<br>2<br>3<br>T<br>i<br>s<br>s<br>u<br>e<br><br>I<br>D<br>U<br>A<br><br>a<br>c<br>t<br>i<br>v<br>i<br>t<br>y<br>(<br>n<br>m<br>o<br>l<br>/<br>m<br>g<br><br>p<br>r<br>o<br>t<br>e<br>i<br>n<br>/<br>h<br>)<br>Bone Joint Cartilage |
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| Page 32 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Academic<br>Partnerships with<br>Centers of Research,<br>Translational<br>Science<br>& Clinical Excellence<br>Patient<br>Associations and<br>Advocacy Groups<br>Academic and Development Partners |
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| Page 33 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Patent Estate<br>Patent Status<br>Technology Platform Patent: • WO2013092922 (Published June 2013)<br>• National Phases granted<br>GLB1 Program: • WO2018122746A1 (Published July 2018)<br>• National Phases filed<br>GBA1 Program:<br>• WO2018122775 (Published July 2018)<br>• National Phases filed<br>• PCT application filed (to be published May 2021)<br>GALC Program: • PCT application filed (to be published May 2021)<br>IDUA Program: • Provisional patent (Filed February 2020)<br>• PCT application to be filed (February 2021) |
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| Page 34 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>2021<br>2022<br>Morquio B / GM1 Gangliosidosis: IND filing<br>Gaucher / Parkinson’s Disease: IND filing<br>Krabbe: Animal Proof of Concept<br>MorquioB / GM1 Gangliosidosis: Animal POCs – completion (Q3), IND-enabling studies – initiation (Q4)<br>Gaucher / Parkinson’s Disease: Animal POC – completion (Q3), IND-enabling studies – initiation (Q4)<br>Krabbe: Lead Optimization & Characterization<br>2023<br>Upcoming Milestones<br>Morquio B / GM1 Gangliosidosis: Start of clinical studies<br>Gaucher / Parkinson’s Disease: Start of clinical studies<br>Krabbe: IND filing |
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| Page 35 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>* Data provided by S&P CapIQ and Company Websites as of October 22, 2020<br>** Grandview Market Research Report, Published Oct, 2019. “Enzyme Replacement Therapy Market Size, Share & Trends Analysis By Enzyme (Pancreatic Enzymes, Agalsidase Beta), By Therapeutic Condition (Gaucher, Fabry, Pompe, MPS),<br>By Route of Administration, By End Use, And Segment Forecasts, 2019 – 2026”<br>† www.fortunebusinessinsights.com/industry-reports/neurodegenerative-diseases-drugs-market-100661; 2026 is estimated<br>$35.5B<br>$62.8B<br>Global Neurodegenerative<br>Diseases Drug Market†<br>2018 2026<br>7.4% CAGR Gene Therapy, Chaperones, & Others*<br>Enzyme Replacement Therapy (ERT)*<br>$6.7B<br>$12.1B<br>7.7% CAGR<br>Global ERT Sales**<br>2018 2026<br>Diversified Pipeline Targeting Multi-Billion Dollar Markets |
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| Page 36 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Research Funding & Grants: Originally established in Switzerland in 2017 as Gain Therapeutics, SA with 16<br>employees in Lugano, Switzerland, Barcelona, Spain – HQ in Bethesda, Maryland<br>Completed $10m Series B Financing in July 2020<br>Completed $46m IPO in March 2021, led by BTIG and Oppenheimer & Co<br>Awarded funding support from The Michael J. Fox Foundation for Parkinson’s<br>Research and The Silverstein Foundation for Parkinson’s with GBA<br>Collaborations with Sumitomo Dainippon Pharma Co and Zentalis Pharmaceuticals<br>Financing History and Stakeholders |
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| Page 37 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Eric I. Richman<br>CEO and Member<br>Khalid Islam, PhD<br>Founder and Chairman<br>Dov Goldstein, MD<br>Independent Member<br>Gwen Melincoff<br>Independent Member<br>Claude Nicaise, MD<br>Independent Member<br>Hans Peter Hassler<br>Independent Member<br>Jeffrey Riley<br>Independent Member<br>Strong Board of Directors - (>$30B in transactions) |
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| Page 38 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Ana Maria Garcia<br>Collazo, PhD<br>Head of Research<br>Roberto Maj, PharmD<br>Head of Development<br>Xavier Barril, PhD<br>CSO<br>Manolo Bellotto, PhD<br>President & General<br>Manager<br>Eric I. Richman<br>CEO<br>Salvatore Calabrese<br>CFO<br>Experienced Management Team - Extensive biotech and pharma experience (>$3B transactions) |
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| Page 39 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Joanne Taylor, PhD<br>Advisor<br>Michel Vellard, PhD<br>Advisor<br>Lorenzo Leoni, PhD<br>Advisor<br>Samuel Broder, MD<br>Advisor<br>Diverse Group of Scientific Advisors |
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| Page 40 © 2021 - GAIN THERAPEUTICS Corporate Presentation<br>Platform Technology<br>Robust Pipeline<br>Upcoming Milestones<br>• Proprietary and patented SEE-Tx platform identifies allosteric (non-catalytic) binding sites in proteins and<br>enzymes that can regulate proper protein folding to restore functional activity<br>• Convergence of Computational Biology and Supercomputing<br>Therapeutic Focus<br>• Demonstrated targeted engagement<br>• Strong intellectual property estate-5 new NCE families patented<br>Global Partnerships • Strong relations with academic centers, key patient associations, and development partners<br>• Partnership established with Sumitomo and Zentalis with potential to establish additional partnerships<br>Team • Seasoned and experienced management team, board of directors and scientific advisors<br>• Near term milestones: several development candidates currently completing animal POC<br>• IND enabling studies starting 2021<br>• Addressing Protein Misfolding by identifying and targeting novel previously undruggable allosteric binding sites<br>• Initial focus on lysosomal storage and CNS diseases -- large & growing markets with unmet medical need<br>Executive Summary |
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