compromising the immune response - alma...

PROPRIETARY ALMA BIO THERAPEUTICS

Alma Bio Therapeutics Treating Autoimmune Diseases Without Compromising the Immune Response

February 2017

Novelty


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


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


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



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



Reinstating Strict Control

Control over the inflammatory response is reinstated by directing potent regulatory T cells to sites of local inflammation in the body


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


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



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



Proof of Concept and Efficacy

Alma's Treatment Significantly Reduces Inflammation of the Colon

SickAcute IBD

TreatedHSP90

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Normal /Healthy

SICK

TREATED

NORMAL



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



New Drug Targets for Crohn's Disease

Anti-TNF

Anti-adhesionmolecules

Downstream signalingblockade

Immunomodulator

IL inhibitor

Cytokine

Launched


Competition

All these drugs and candidates in the pipeline are small molecules or biologics that suppress pro-inflammatory mediators


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



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



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



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



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



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



€ 2.2 M

current state

Network and Collaborations

Science :

Technology:

Network:

Financial Support:

Legal And Accounting :



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



Contact: [email protected]

, 3 new applications

compromising the immune response - alma...

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