Changing Lives Through Precision Oral Medicines - October 2024 - Jubilant Therapeutics
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Changing Lives Through
Precision Oral Medicines
October 2024
1
Disclaimer
Statements in this document relating to future status, events, or circumstances, including but not limited to statements
about plans and objectives, the progress and results of research and development, potential product characteristics and
uses, product sales potential and target dates for product launch are forward-looking statements based on estimates and
the anticipated effects of future events on current and developing circumstances. Such statements are subject to
numerous risks and uncertainties and are not necessarily predictive of future results. Actual results may differ materially
from those anticipated in the forward-looking statements. Jubilant Therapeutics may, from time to time, make additional
written and oral forward looking statements, including statements contained in the parent company (Jubilant Pharmova)
filings with the regulatory bodies and its reports to shareholders. The company assumes no obligation to update forward-
looking statements to reflect actual results, changed assumptions or other factors.
2
Non-Confidential
Mission and Therapeutic Focus
OUR MISSION is to transform the lives of patients through the development of
precision oral medicines with enhanced safety and therapeutic efficacy
Hematology/Oncology
Solid Tumors
Immunology
3
Non-Confidential
Company Highlights
Clinical-stage precision therapeutics company founded in 2019 to discover and develop therapeutics with
meaningfully improved safety and efficacy profile against first-in-class and validated but intractable targets
Pipeline generated through in-house Therapeutic Index and Brain Exposure
Optimization (TIBEO) discovery engine, validated through partnerships
Independent management and board backed by Jubilant Pharmova–
a global healthcare organization committed to funding through proof-of-
concept trials
Near-Term Milestones JBI-802 coREST inhibitor in Phase 2 development for hematology
and solid tumors; JBI-778 PRMT5 Inhibitor in Phase 1 development
• JBI-802 and JBI-778 for solid tumors
early data readout by
mid 2025 FDA Orphan drug designations for JBI-802 and JBI-778
4
Non-Confidential
TIBEO Advanced Discovery Engine Enhances the Therapeutic Index and
Optimizes Brain Penetration
Site-
specific
targeting
Selectivity Mutation
screening driven cell
screening Developing First-in-Class,
Structure-Based Drug Design: Unique &
Validated Intractable Drug
Computational Modelling Proprietary
Targets in Genetically-Defined
& Genetic Signatures Scaffolds
Patient Populations
ADME
Toxicology brain focus
Genetically-
defined
patient
selection
Jubilant’s discovery engine is based on a drug discovery approach validated through 75+
integrated discovery programs for big pharma, biotech, and healthcare VC and has a team of
dedicated scientists
5
Non-ConfidentialDiverse Clinical Stage Pipeline with Improved Therapeutic Index for
Multiple Cancer Indications and Patient Subsets
Program Mechanism Indications Lead Optimization Pre-Clinical (IND) Phase I/II Milestones
ET/MPN (resistant to ✓ Company sponsored trial
cytoreductive ▪ Interim Phase II Data –
therapy)
mid 2025
CoREST
JBI-802 mSTK11 IO
Inhibitor
Resistant
NSCLC
▪ Investigator led Phase II
Trials under planning
Post MPN AML
PRMT5
Inhibitor
Brain EGFR mut NSCLC, ✓ Company sponsored trial
JBI-778 Penetrant mIDH high grade ▪ Interim Phase I Data –
(MTAP+/-, glioma, ACC
mid 2025
spliceosome
selective)
ET – Essential Thrombocythemia; MPN: Myeloproliferative Neoplasm; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; AML – Acute Myeloid
Leukemia; MTAP: Methylthioadenosine phosphorylase, EGFR: epidermal growth factor receptor, mIDH: isocitrate dehydrogenase (IDH) mutation, ACC: Adenoid
6 Cystic Carcinoma, STK: serine/threonine kinase; IO: Immuno-oncology
Non-ConfidentialAdditional Preclinical Stage Pipeline including First-in-Class Targets such
as PAD4
Program Mechanism Indications Lead Optimization Pre-Clinical (IND) Phase I/II Milestones
PD-L1 Inhibitor Brain tumor and
JBI-2174
metastases
IND track
Brain Penetrant
Oncology and auto-
JBI-1044 PAD4 Inhibitor
immune disease
IND track
Other Various Various Undisclosed research programs
EGFR1,* Oncology
BRD4* Oncology
• 1Blueprint Medicines acquired Lengo Therapeutics (Frazier Healthcare entity) for $250M in cash plus $215M in milestone payments
7
• *Economic rights reside with Jubilant Therapeutics' parent company
Non-ConfidentialCoREST Inhibitor Lead Program
JBI-802
Epigenetic
Modulating Multiple Development Opportunities in
Agent Hematology/Oncology & Solid Tumors
Non-ConfidentialJBI-802 Represents Significant Development Opportunity
in Hematology and Solid Tumors
CoREST Inhibitor JBI-802 Offers
Broad Therapeutic Potential
3 • Phase 2 in ET and MPN with thromocytosis
• Phase 2 in STK11-mutant NSCLC
• Phase 2 in Erythroleukemia (Post MPN AML)
2 • Potential to reverse resistance to immunotherapy in solid tumors due to STK11 mutations
• Confirmed partial response in doublet IO refractory STK11-mutant NSCLC patient with
JBI-802
Pancoast syndrome
Potential for superior efficacy and safety compared to LSD1 only inhibitor in hematology/ oncology
1 • Human POP with dose dependent reduction in platelet levels
• Faster reduction of platelets (~10 days* compared to ~10 weeks**)
• Does not induce dysgeusia or anemia in patients*
• Significant efficacy in post-MPN leukemia (erythroleukemia) model leading to orphan status by FDA
ET – Essential Thrombocythemia; MPN: Myeloproliferative Neoplasm; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer; AML –
9 Acute Myeloid Leukemia; dysgeusia – condition that affects sense of taste, impacting appetite and quality of life
Non-ConfidentialFirst-In-Class CoREST Inhibitor JBI-802 Can Potentially
Address Significant Unmet Medical Need
Blood cancer causes bone marrow to produce too many platelets leading to stroke and heart
ET/MPN attack and eventually cancer – chronic condition requiring long term therapy
Blood Disorders Potential better safety and efficacy than Bomedemstat (Merck – Phase III)
Leading to Cancer Commercial validation - Merck acquired Bomedemstat for $1.35B
Unmet need for efficacious therapy for refractory/non-responders to current therapies
~100k Patients (cytoreductive)
Phase II Interim Data – mid 2025
MPNs are blood cancers that cause increased production of blood cells, mainly affecting red
Post MPN AML blood cells, platelets, or white blood cells.
Leukemia Progression from MPN to AML (Acute Myeloid Leukemia) is a serious complication, occurring
in MPN patients.
~3- 5% of 265k High-unmet need for effective therapy with survival only for 5 months
MPN patients Investigator led trial under planning
Demonstrated clinical efficacy in JBI-802 in one patient (Phase I study)
NSCLC
Disease with high-unmet need with no effective therapy
Lung Cancer
Patients with STK11 mutations have a lower survival rate and are resistance to immune
checkpoint therapy (like Keytruda, Atezolizumab)
~10% of 300k+ Investigator led trial under planning
NSCLC Patients; Additional upside in SCLC patients ~ 10-15% of lung cancer (JBI-802 achieved tumor
regression in combination with PD-1 inhibitors in animal models)
10
Non-Confidential 10
ConfidentialJBI-802 Induces Differentiation and Cell Death of
MPN/Leukemia Progenitors
Percent cells expressing CD86
16
14
LSD1i
% Positive cells
12
CoREST 10
Megakaryocyte 8
HDAC6 Erythroid progenitor 6
LSD1 4
2
Megakaryocyte Platelets
Response Control
Elements
0
Control PMA HDAC6i LSD1i JBI-802
JBL-LSD1-HDAC6
Dual Inhibitor
Percent cells expressing CD235
16
14
12
% Positive cells
Erythrocyte
HDAC6i 10
8
6
4
2
0
Control PMA HDAC6i LSD1i JBI-802
LSD1 and HDAC6 are part of the coREST complex that drives tumorigenesis of lineages like platelet and erythroid (MEP),
thereby creating opportunities for synergistic targeting these REST-driven tumors
11
Non-ConfidentialKey Findings from Phase I Trial of JBI-802
• Dose-Proportional Exposure and Platelet • Tumor-Related Symptom Improvements and Partial
Decrease Correlation Response
The study observed a dose-proportional increase Among the non-small cell lung cancer (NSCLC) patients with
in exposure across cohorts, with a direct resistance to immuno-oncology (IO) treatment, 2 out of 2
correlation between exposure levels and on-target patients showed improvements in tumor-related symptoms,
platelet decrease, suggesting a dose-dependent with one confirmed partial response (~39% tumor
biological effect. shrinkage and patient stable for over 12 months),
suggesting potential efficacy in this challenging patient
population.
• 10mg Dose Safety and Biological Activity • Symptom Improvements Without Thrombocytopenia
The 10mg dose was well-tolerated, with no Improvements in tumor-related symptoms without any
significant platelet decrease observed, while still negative impact on platelet levels, further supporting the
exhibiting biological activity, indicating a favorable favorable safety profile of the investigational drug.
safety profile at this dose level.
12
Non-ConfidentialHuman Proof of Principle for JBI-802 Indicates Faster Onset of Clinical Activity
than LSD1 Only Inhibitor – Suited for ET, MDS/MPN with Thrombocytosis
JBI-802 platelet levels Bomedemstat (LSD1 only inhibitor) platelet levels
Merck acquired Imago Biosciences
(Bomedemstat) for $1.35B based on
Phase II data in ET
• Prelim human data confirms JBI-802 can induce dose dependent decrease in platelets without effect on erythroid
parameters – Proof of Principle for treatment of diseases with elevated platelets like ET, MDS/MPN with thrombocytosis
• JBI-802 demonstrates superior efficacy and safety compared to LSD1 only inhibitor
• Induces faster reduction of platelets (within ~10 days* compared to ~10 weeks**)
• Does not induce Dysgeusia in patients* (compared to 55% incidence**)
• Does not induce Anemia in patients and in animals* (compared to 16% incidence**)
13 *JBI-802 Phase I trial – basket tumor patients **Bomedemstat Phase II trial – ET patients
Non-ConfidentialJBI-802 NCLC Patient with STK11 Case Study
Patient with NSCLC, just coming off from Nearly 1.5 years in the study,
double immunotherapy (Opdivo+Yervoy: Pancoast symptoms
IO non responder) after progression – last disappeared, “patient is doing
stage with only hospice care option. very well with no issues”. Post-
Pancoast syndrome -tumor pressing on treatment 3rd scan showed a
nerves causing incredible pain and 39% tumor reduction confirmed
inability to use arm. Patient has STK11 by the 4th scan in May 2024
mutation which is thought to confer and confirmed PR with stable
resistance to immunotherapy disease as of Oct 2024
Enrolled in JBI-802 study with
initial treatment in May 2023
• STK11 induced resistance can potentially be reversed by a combination IO + CoREST inhibitor; Investigator
proposing a follow-up investigator trial of JBI-802 in combination with anti-PD-1 (Keytruda) in STK11 mutant
NSCLC
JBI-802 Phase 1 Results Show Therapeutic Potential in
Sensitizing Immunotherapy Resistant Tumors
14
Non-ConfidentialClinical Development Pathway for JBI-802 in Hematology
and Solid Tumors
Phase I Dose escalation Phase II Potential regulatory pathway
Accelerated ET/MPN with thrombocytosis
dose 2nd line ET/ MPN,
MTD
RP2D
escalation post MPN AML
(basket trial) Erythroleukemia/post-MPN AML
Established prelim proof of
principle for dose dependent
platelet decrease and reversing
STK11 resistance to IO therapy
in NSCLC
JBI-802 + Anti-PD-1
NSCLC IO resistant /refractory IO refractory NSCLC
2nd line SCLC
JBI-802 + Anti-PD-L1
SCLC IO resistant /refractory
MPN: Myeloproliferative neoplasms; SCLC: Small cell lung cancer; NSCLC: non small cell lung cancer; ET: Essential Thrombocythemia; AML: Acute Myeloid
15 Leukemia; IO: Immuno-oncology; RP2D: Recommended Phase II dose
Non-ConfidentialPRMT5 Inhibitor
JBI-778 for Solid Tumors
Brain
Penetrant
Phase 1 ready for EGFR mut NSCLC,
Agent mIDH high grade glioma, ACC
Non-ConfidentialJBI-778 Shows Potential as Best-In-Class PRMT5 Inhibitor
with Superior Brain penetration
• Oral, highly differentiated, SAM cooperative brain penetrant PRMT5 inhibitor
3 • Addresses both MTAP +/- tumors
• IND approved, Phase 1 ready
2 • IND enabling 4-week GLP tox studies completed in rats and dogs
• No mortality in either animal species even at the highest dose
• No effect on platelets
• Drug product manufacturing completed at Catalent
1 • PRMT5 is highly overexpressed in many human cancers
• Glioblastoma (GBM) with splicing dysregulation is selectively sensitive to inhibition of PRMT5
• 3rd Gen EGFRi resistant tumors have enriched RBM10 mutation which are sensitive to PRMT5 inhibition
MTAP: Methylthioadenosine phosphorylase; SAM: S-adenosyl-methionine; EGFR: epidermal growth factor receptor
17
Non-ConfidentialSignificant Opportunity for JBI-778 to Address Unmet Medical
Need in Difficult-to-Treat Cancers (MTAP +/-)
NSCLC High-unmet need with no effective therapy for 3rd Gen EGFRi resistant NSCLC
Lung Cancer Genetically defined patient stratification
Preclinical studies suggest an optimal therapeutic window with demonstrated better
safety
~10% of ~300k +
NSCLC Patients US FDA approved IND, first-in-human trial in India
HGG
IDH+ HGG sensitive to PRMT5 inhibition
Brain Tumor
High unmet need with no treatment option for recurrent HGG
2.5% of ~61k + Brain
Cancer Patients
Adenoid cystic tumors enriched with specific mutations and are highly sensitive to
ACC PRMT5i
Head & Neck cancer High unmet need with chemotherapy as the only current treatment option after
surgery and radiation, with low efficacy
Interim Data – early 2025
Patient Data – US region; NSCLC: non-small cell lung cancer; HGG: High grade Glioma; ACC: Adenoid Cystic Carcinoma; IDH: Isocitrate
18 dehydrogenase; EGFR: epidermal growth factor receptor
Non-ConfidentialJBI-778 Oral, Highly Differentiated, Substrate Competitive
PRMT5 Inhibitor
Safe and well tolerated in 4-week GLP tox study with no thrombocytopenia
Bareketain et al. Nature Com 2021
Binding site for SAM
cooperative and substrate
competitive inhibitor
(JBI-778) Binding site for SAM
competitive inhibitors
(high toxicity seen)
Different binding and MOA with potential to be less toxic in clinic
19 MOA: mode of action; SAM: S-adenosyl-methionine
Non-ConfidentialJBI-778 vs. Competitive PRMT5 Inhibitors
Jubilant Therapeutics
Company Tango, Mirati, Amgen Pfizer, Prelude, J&J
(JB-778)
✓ Substrate competitive
✓ SAM Cooperative
Product Type ✓ MTA Cooperative ✓ SAM Competitive
✓ Spliceosome Selective
✓ Brain Penetrant
▪ Targets substrate site and ▪ Stabilizes MTA bond to PRMT5 ▪ Blocks the binding of SAM cofactor
stabilizes SAM bond to PRMT5 which is increased in MTAP- shared among many other
Mechanism of with high biological selectivity deficient tumor methyltransferases
Action ▪ Opportunity for
▪ Brain penetration in primary patient selection and
tumors as well as brain reduction in toxicity
metastases
▪ Address safety issue of 1st ▪ MTAP deficiency is present in ▪ Blocks a non-selective cofactor
generation ~10% patients and may not be which could explain non-tolerable
applicable to brain since MTA is toxicity
▪ Targets broad patient metabolized in brain
Challenges population irrespective of MTAP ▪ Limited patient selection strategy
status
▪ Spliceosome-based patient
selection
Development IND approved; Phase I/II ready Phase I/II Phase I/II terminated due to toxicity
Stage and limited efficacy
20
Non-ConfidentialJBI-778 Demonstrates Potent Anti-Tumor Responses
In vivo Target Engagement Tumor size after treatment with JBI-778 and GSK3326595 in a
systemic lymphoma xenograft model (Z138)
nograft model Z-138 xenograft tumors
D mice ELISA
% SDMA/SmD3 of Vehicle
150
0 mpk 100
SDMA
k
50
pk
SmD3
0
-Tubulin
ID i
, Q 5i
le
, B 95
,B 5
D
ic
pk T
pk T
J ID
pk 5
m M
0m RM
eh
m 26
50 PR
50 33
V
10 JP
-
K
S
G
Significant reduction of SDMA level
0 15 20
observed in the in vivo study
ment initiation
Superior tumor inhibition in systemic
ED50 < 10 mg/kg BID
tumor model vs GSK3326595
21
Non-ConfidentialJBI-778 extends survival in preclinical models for
Glioblastoma
JBI-778 treatment results in much less
Survival Plot: U87MG Orthopedic Study
Vehicle control tumor burden on 005 GBM
JBI-778-50mpk BID
GBM 005 animal model is among the
best representation of the human
glioblastoma tumor available
22
Non-ConfidentialJBI-778 Clinical Development Strategy
Phase I Dose escalation Phase II Potential regulatory pathway
mEGFR NSCLC TKI refractory with/
Accelerated without brain mets mEGFR NSCLC TKI
dose MTD
RP2D* refractory, mIDH HGG,
escalation mIDH High Grade Glioma and ACC ACC
Potential for accelerated approval
based on ORR in single arm trial
*Optimal dose based on PK/PD/Efficacy
IND cleared by FDA; FIH in 2024
NSCLC: Non-small cell lung cancer; ACC: Adenoid cystic carcinoma; HGG: High grade Glioma; IDH: Isocitrate dehydrogenase; EGFR: epidermal growth factor
23 receptor; TKI – Tyrosine Kinase Inhibitors; FIH: First in human
Non-ConfidentialExecutive Leadership Driven by Scientific Excellence to
Develop First in Class Therapeutic Targets
SYED KAZMI, PhD, MBA MELDA DOLAN, MD SHYAM PATTABIRAMAN, MS SRIDHARAN RAJAGOPAL, PhD
Chief Executive Officer Chief Medical Officer Chief Financial Officer VP & Head,
Medicinal Chemistry
Scientific Advisory Board:
Dr. Ross Levine Laurence Dr. Santosh Kesari Dr. William C. Hahn Dr. Neal Rosen
Joseph Dineen Chair in Leukemia Director, Neuro-Oncology; Professor, Dept. William Rosenberg Professor of Enid A. Haupt Chair in
Research; Chief, Molecular Cancer of Translational Neurosciences; Director, Medicine Medical Oncology, MSKCC
Medicine Service, HOPP MSKCC Research Clinical Institute, Providence Interim EVP & COO, CSO, Dana-
Southern California Farber Cancer Institute
24
Non-ConfidentialUpcoming Milestones and Catalysts
2H 2024 mid 2025 2H 2025
JBI-802 Ph II JBI-802 Ph II early data JBI-802 Ph II early JBI-802 Ph II
in ET/ MPN, in ET/ MPN; data from select completion in
Ph II investigator led trial in multiple indications
investigator led investigator led trials
NSCLC trial post MPN AML, SCLC
JBI-778 Ph I JBI-778 IND for PD-L1i, JBI-778 Ph I
in EGFR mut NSCLC, completion/ Ph II
early Ph I PAD4i
start in multiple
mIDH high grade data indications
Glioma, ACC
2024 2025 2026
25
Non-ConfidentialSummary
Clinical-Stage Precision Oral Medicine Company Aiming to Improve Patient
Outcomes in Hematology Oncology, Solid Tumors, and Immunology
JBI-802 in Phase 2 Clinical JBI-778 in Phase 1 Value inflection potential with
Trial with Preliminary Clinical Trial de-risked clinical data
Results expected by
mid 2025
26
Non-Confidential 26Thank You
Syed Kazmi, CEO
Syed.kazmi@jubilanttx.com
Shyam Pattabiraman, CFO
Shyam.Pattabiraman@jubilanttx.com
Jubilant Therapeutics Inc.
790 Township Line Road, Suite 325.
Yardley, PA 19067,USA
Ph: (215) 550-2810
https://www.jubilanttx.com
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