1. Valued
Added
Solu+ons
for
Orphan
Disease
Trials

2. 2
Max Neeman’s Value Added Solutions
q Access to proprietary databases and key investigators
q Built a network of referring physicians to have access of few
patients who are spread over a large geographic area
q Partnership with relevant patient advocacy groups
q Patient Home Support system: a network of GCP trained CRCs/
nurses travel to patient’s home and administer drug infusion,
conduct blood draws, PK sampling or clinical test as per the protocol,
resulting in less travel and hence patient retention
q Pan India presence with local network of CRAs & CRCs helps to
commit more resources per site, when required
q Creation of platform to share knowledge base with both participating
investigators & clinical trial participants; keeps patients &
stakeholders motivated

3. 3
Orphan Drug Experience
q Max Neeman has conducted >15 orphan drug designated
studies, in various indications including Hemophilia, Von
Willebrand and Lysosomal storage disorders
q Max Neeman has an established team specialized in carrying out
orphan drug trials in response to sponsor need
q Max Neeman Project Managers have 10+ years of industry
experience and a history of successfully completed, difficult to
execute rare disease global trials
q Max Neeman has an extensive database of research oriented
investigators with expertise in genetics
q Max Neeman conducted 3 rare disease global trials successfully
audited by USFDA for highest enrolment globally

4. q Per the Drug & Cosmetics Act, if a new drug is approved and
marketed in a well-regulated country, marketing authorization
can be obtained in India with waiver of clinical trial in Indian
population.
§ Such a wavier can be considered in cases of emergency,
extreme urgency and for orphan drugs or drugs indicated
for conditions/diseases with no therapy option.
q 400 USFDA approved orphan drugs and 90 EMA approved
orphan drugs are available in India
q In 2014 two new drugs in India, targeted at T-cell lymphoma
and Hemophilia B, got a clinical trial waiver considering their
orphan drug status
4
India’s Positive Regulatory Outlook

5. 5
Challenges in Rare Disease Studies
q Recruitment & Retention Challenges
§ Paucity & scattered rare disease patients across the country
§ Stringent inclusion/exclusion criteria
§ High frequency of site visits and multiple medical
assessments prove to be a barrier for patients who have to
travel hundred of miles for clinical trials
§ Counterproductive to rely on few sites in metropolitan cities
q Identifying & Setting up of Sites
§ Poorly Maintained database of patients
§ Proper identification of KOLs as knowledge base in rare
disease is scattered
§ Ability to develop and train sites throughout
§ Resource crunch at sites when most required

6. 6
Orphan Drugs / Rare Diseases
Definitions
q Diseases affecting a small percentage of the population
q The World Health Organization – Pathological conditions affecting
0.65-1 out of every 1000 inhabitants
q European Union – Diseases with a prevalence of 5:10,000 Europeans
q USA – Ailment affecting fewer than 2,00,000 Americans (with an
incidence of less than 1/5,000 in the general population)
q Japan – Disease affecting less than 50,000 Japanese patients
(or 1 in 5000 general population)
q Australia – Disease affecting less than 2000 Australian patients
q Ultra orphan disease - prevalence of less than 0.18 case per 10,000
population
q 5,000 and 7,000 distinct rare diseases*
q 80% of rare diseases – Genetic origin
q 20% of rare diseases – Other causes (infections/ allergies/
degenerative/ proliferative)
q Orphan Drugs – Drugs for treatment of rare diseases

7. 7
MNI Therapeutic Experience
Orphan Indications
q Hemophilia [A&B]
q Von Willebrand Disease
q Lysosomal Storage Disorders
q Multiple Myeloma
q Thrombocytopenia
q Congenital Fibrinogen Deficiency
q Congenital Afibrinogenaemia
q Multiple Sclerosis
q Huntington’s Disease
q Gaucher’s Disease
q Fabry’s Disease
q Duchenne Muscular Dystrophy

8. 8
Case Studies
#1 Study title: Inhibitor development in previously untreated patients
exposed to factor VIII concentrates and to recombinant factor VIII concentrates
q Indication: Hemophilia A
q Design: Multi-centre, Prospective, Controlled, Randomised, Open Label
q Phase: III
q Number of Patients: 300
q Number of Centres: 9 (India) / 82 (Global)
q Status: Follow up Phase
#2 Study title: A clinical trial to study the efficacy and safety of XXX for on-demand
treatment of acute bleeding and to prevent bleeding during and after surgery in subjects
with congenital fibrinogen deficiency
q Indication: Congenital Fibrinogen Deficiency
q Design: Prospective, open-label, uncontrolled, phase III study to assess the efficacy
and safety
q Phase: III
q Number of Patients: 8 (India) / 24 (Global)
q Number of Centres: 5 India
q Status: Pre-Study
*Indian Council of Medical Research

9. 9
Case Studies
#3 Study title: An open-label, multi-center, safety and efficacy, phase III study
of a recombinant coagulation factor IX
q Indication: Hemophilia B
q Design: Prospective, multicenter, non-randomized, open-label, safety and efficacy
Phase III study of rIX-FP
q Phase: III
q Number of Patients: 40
q Number of Centres: 6
q Status: Follow up Phase
#4 Study title: Immunogenicity, efficacy and safety of treatment with human-cl rhFVIII
in previously untreated patients with severe Hemophilia A
q Indication: Severe Hemophilia A
q Design: Prospective, multicentre, multinational, open-label, non-controlled
q Phase: III
q Number of Patients: 40 (India)
q Number of Centres: 20
*Indian Council of Medical Research

10. 10
Hemophilia
q Recessive X – linked bleeding disorder
q Clotting factor deficiency
q Affects males; females are carriers
q Hemophilia A (Classical Hemophilia)
q Clotting factor VIII deficiency
q 1 in 5,000–10,000 male births (80%)
q Hemophilia B (Christmas Disease)
q Clotting Factor IX deficiency
q 1 in about 20,000 - 34,000 male births (20%)
q 1330 hemophilic children are born every year in India*
*Indian Council of Medical Research

11. 11
Multiple Myeloma
q Cancer of plasma cells
q Incidence - 1 to 4 per 100,000 people per year
q More common in men
q Most common primary malignant tumor of the bone;
about 27% of biopsied bone tumors
q Second most common hematological malignancy
(13%)
q Constitutes 1% of all cancers
q 5 year survival rate

12. 12
Multiple Sclerosis (MS)
q Nervous system disease affecting brain and spinal cord
(myelin sheath damage)
q Optico-spinal phenotype (attacks are mostly confined to optic
nerve and spinal cord) – more prevalent in India
q Prevalence in Indian subcontinent - 1.3/100,000
q Highest incidence in Parsi community of India
q HLA-B12 associations - highly reported in Parsi community of India
q Maximum cases between 3rd and 4th decade
q Cognitive dysfunction in MS - 40 to 60%
q 0.32 to 1.58% of neurology admissions in Indian hospitals
q Hospital in patient statistics in India - Approx fourfold increase in
admitted MS cases over the last decade
q Increase in MS diagnosis
§ Increasing awareness of medical illnesses,
§ Availability of modern investigative facilities (MRI, evoked potential studies
and immunoglobulin estimation)
§ Expanding neurological services in India

13. 13
Huntington’s Disease
q Rare, incurable, adult-onset, autosomal dominant
inherited disorder
q Cell loss within a specific subset of neurons in the
basal ganglia and cortex
q Characterized by involuntary movements (chorea),
dementia, and behavioral changes
q Worldwide prevalence - 5-10 cases per 100,000
persons
q Juvenile HD – 10% of all the cases
q Life expectancy – approx. 20 years following the onset
of visible symptoms
q Associated morbidity – pneumonia, heart diseases,
psychiatric disorders (suicide)

14. 14
Gaucher’s Disease
q Most common lysosomal (lipid) storage disorder
q Inborn error of metabolism; autosomal recessive
q Deficiency of the enzyme glucocerebrosidase
q Three main types
§ Type I – Non Neuronopathic (Most Common)
§ Type II - Acute Neuronopathic
§ Type III - Chronic Neuronopathic
q Rare in the non-Jewish population - 1 per 40,000
population
q In Jewish people of eastern European origin
§ Carrier frequency -1 per 15 population
§ Disease frequency - 1 per 855 population

15. 15
Fabry’s Disease
q X linked recessive disorder
q Deficiency of the enzyme alpha galactosidase A
q Clinical abnormalities of skin, eye, kidney, heart,
brain, and peripheral nervous system
q Estimated incidence –
§ 1 in 40,000 males
§ 1 in 117,000 in the general population
q Death - by 4th or 5th decade of life (renal failure,
heart failure, or strokes)

16. 16
Duchenne Muscular Dystrophy (DMD)
q Most common Muscular Dystrophy
q Severe Recessive X-Linked Disorder
q Characterized by Muscle Weakness
q Affects one in 3500 males
q Caused by mutations in the dystrophin gene –
q deletions (60-65%)
q point mutations (30-40%)
q duplications (5-6%)
q Deletion rate reported in Indian studies – 63-74%

17. 17
To Learn More
Contact Information:
Ann Vawter
Director, Business & Marketing
Max Neeman International
117 Edinburgh South Dr., Ste 105
Cary, NC 27511
P: 919.424.3332 / F: 919.852.5574
E: ann.vawter@neeman-medical.com
www.neeman-medical.com