PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics Treating Autoimmune Diseases Without Compromising the Immune Response
February 2017
Novelty
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Alma is working to provide a cure for people who suffer from autoimmune diseases
The challenge requires a completely new approach to therapy
Our approach attempts to tilt the balance away from the harmful inflammation associated with autoimmune diseases and toward resolution and healing
PROPRIETARY ALMA BIO THERAPEUTICS
A Case of Mistaken Identity
From time to time the immune system mistakenly views the body's own cells and tissues as harmful foreign invaders, and attacks
• Over 90 different autoimmune diseases
• More than 100 million patients worldwide
• 20 million patients in Europe
• 4.5 million in France
• Incidence and prevalence on the rise, not only in the western world
• Global annual cost of care > € 120 billion
MS - Multiple sclerosisRA - Rheumatoid arthritis
Alma Bio Therapeutics
Current Treatments:
• Suppress symptoms, do not focus on the cause of disease
• Address a single drug target
• Do not address the complexity of the disease process
• Efficacy and tolerance vary - unpredictable side effects, often severe
• Up to 30% of new patients do not respond; up to 40% becomerefractory with time
There is urgent need for a curative treatment with limited adverse effects, suitable for most patients
Immune modulators are blockbusters in the making
The Need
None of the Current Treatments Provide a Cure
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
The Underlying Mechanismsof Autoimmune Disease
The function of the immune system is to maintain a fine balance within the body
• It continuously monitors the body• If necessary it initiates a local contained inflammatory response as a
corrective action• Powerful regulatory white blood cells known as Treg keep this
corrective action under strict control
Loss of strict control leads to autoimmune disease
• LOCAL Treg malfunction is like brake-failure in a car• The immune system runs wild and cannot slow down• Inflammation becomes pathologic and results in autoimmune disease
Treg
Treg
Regulated Inflammation
Uncontrolled Inflammation
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Reinstating Strict Control
Control over the inflammatory response is reinstated by directing potent regulatory T cells to sites of local inflammation in the body
PROPRIETARY ALMA BIO THERAPEUTICS
Alma has discovered that Heat Shock
Proteins (HSP), a highly important
family of body molecules, recruit Treg
cells from the circulation, boost them
and direct them to sites of inflammation in the body
This is the basis of Alma's therapeutic approach
Alma Bio Therapeutics
Treg
Treg
TregTreg
Treg
Treg Blood Vessel
HSP
Recruitment of Tregs
1| Disease
3| Resolution2| Treatment
Uncontrolled inflammation
Treg
Treg
Treg
Controlled localized
Inflammation
The Treatment
• Treatment is not a gene therapy
• Plasmid are injected into the muscle: very low doses arerequired to generate a significant therapeutic response
• HSP expression is abundant under conditions ofinflammation
• HSP expression declines once inflammation abates
Alma's treatment is self limiting
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
HSPAlma Bio Therapeutics
Alma's drugs are proprietary plasmids (small circles of DNA) encoding the human immune regulator molecules HSP70 or HSP90
Alma’s ground-breaking technologyis a PLATFORM
Alma addresses Crohn's disease as its first target
One of the two major Inflammatory Bowel Diseases (IBD) that are
chronic, debilitating and currently incurable
• 5.5 million patients w/w
• 2.5 million patients in Europe
• 140.000 patients in France
• The incidence has risen 60% in the last 8 years
• Cost of care in France: € 1.5 billion
The Crohn's drug market will reach € 4 billion in 2022*
* Visiongain, July 2013
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Proof of Concept and Efficacy
Alma's Treatment Significantly Reduces Inflammation of the Colon
SickAcute IBD
TreatedHSP90
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Wal
lace
sco
re o
f co
loni
c da
mag
e
Normal /Healthy
SICK
TREATED
NORMAL
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Mechanism of Action
Alma's Treatment Resolves Inflammation
Decreased Neutrophil migration to colonic tissue
Increased FOXP3+ Treg expression in colon
Increased FOXP3+ Treg expression in mesenteric lymph nodes
Increased IL-10 expression in colon via Tr1 cells
Modulating PGE2 : IL-17 IL-23 Axis
Intellectual Property
7 granted patents, 1 application under evaluation
2 new applications in process
Granted IP originating at the Weizmann Institute of Science The
entire IP estate has been assigned to the company
Broad coverage for treatment of T-cell dependent autoimmune
diseases
Alma's patent attorneys: Europe US
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
New Drug Targets for Crohn's Disease
Anti-TNF
Anti-adhesionmolecules
Downstream signalingblockade
Immunomodulator
IL inhibitor
Cytokine
Launched
PROPRIETARY ALMA BIO THERAPEUTICS
Competition
All these drugs and candidates in the pipeline are small molecules or biologics that suppress pro-inflammatory mediators
Alma Bio Therapeutics
Considerable effort is being invested by Industry and Academia alike to develop new and better treatments for Crohn's disease
None of the above address the need to resolve inflammation by inducing the
expression of pro-resolution mediators
Competitive Advantages
Current
May shift the system further out of control
Variable
Unpredictable side effects
Moderate to severe patients
Chronic administration (daily)
Alma
Restores control without affecting normal immune response
Has the potential of being curative
Self regulating; Minimal side effects are anticipated
Refractory and non-responders
Periodic administration (monthly or longer)
Treatment
Effect on immune fuction
Efficacy
Safety
Positioning
Regimen
Alma's completely new type of treatment promises therapeutic benefits not currently achievable with biologics
Initially it is expected to become a first-line treatment for-non responders and later, for additional under-served patient populations
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Business Model
For each indication Alma will seek to form an alliance with a biopharma company after completion of Phase 2a
The future strategic partners will collaborate on commercialization of
the product including development, regulatory approval and marketing
& sales activities
Autoimmune disease partnerships - comparables
Phase 2a deal terms:
Exclusive worldwide rights, upfront, milestones and royalty payments
• Takeda/ MacroGenics (2014) $469 M
• Roche/ Adheron (2015) $580 M
• Bristol-Myers/ Padlock (2016) $600 M
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
The Team
Prof. Irun R. Cohen, MD,Founder, Inventorand Chief Scientific Advisor
Professor Emeritus of Immunology, Weizmann Institute of Science
ROBERT KOCH PRIZE, AESKU Prize - Life Contribution to Autoimmunity Research
Dr. Binah Baum Founder, Entrepreneur, CEO
Seasoned biotech executive and entrepreneur
Participated in the creation of > 30 start-ups, reaping 6 exits
Dr. Denis Ravel Director, Pre-clinical Development and Regulatory Affairs
More than 30 years as bio-pharma executive, bringing drugs from idea to the clinic
Servier, Genset / MerckSerono, Diatos
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Key Facts
• Founded - Nov 2013
• IP acquired from the Weizmann Institute of Science
• Initially funded by its 3 original founders
• € 1.1 M from business angels
• € 640 K BPI interest-free, non-dilutive loan
• € 110 K BPI PPA interest bearing loan
• € 220 K BPI CMI 2030 phase d'amorcage
• JEI status - May 2014
Alma is pioneering a post-biologics generation of
potentially safe and curative drugs
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Funding - First Target (IBD)
Currently seeking to raise € 300 K jointly with Wiseed: To complete the pilot phase of the regulatory pre-clinical studies
Subsequent funding
Series A round -------------------------- € 4,700 K
► Regulatory preclinical studies* ---- € 2,200 K► Phase I – clinical safety ----------- € 2,500 K
* Completing all pre-clinical regulatory requirements for IND submission,and drug manufacturing, incl. full QC, for phase I.
Series B round -------------------------- € 2,800 K
► Phase 2a - clinical efficacy ------- € 2 800 K
Estimated total investment until a strategic alliance: € 7.5 M
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
2019
Efficacy & mode of action in IBD
models
Regulatory pre-clinical studies; GMP plasmids
for Phase 1
Phase 1:Healthy volunteers
Present round
Phase 2a: Treatment resistant
IBD patients
Completed € 300 K
Alliance
€ 2.5 M € 2.8 M
Development plan
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
€ 2.2 M
current state
Network and Collaborations
Science :
Technology:
Network:
Financial Support:
Legal And Accounting :
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Investment Highlights
o Lucrative market seeking curative drugsPotential curative solution → game changer
o De-risking opportunity at relatively low investmentFirst in man”in one year
o Strong IP estate7 approved patents assigned to the Company
o Viable exit strategy
Collaborative agreement with bio-pharma expected around 2019
PROPRIETARY ALMA BIO THERAPEUTICS
Alma Bio Therapeutics
Contact: [email protected]
, 3 new applications