cytrx (cytr) corporate presentation · ovarian 73% 9% renal 14% 0% h&n 20% 60% cr pr ncslc 45%...
Post on 05-Oct-2020
1 Views
Preview:
TRANSCRIPT
Corporate Overview
May 2019
www.centurionbiopharma.com
Non-Confidential
The World’s Leading
Company Targeting
Albumin To Kill Solid
Tumors
1
Centurion BioPharmaHighlights
▪ Centurion BioPharma is a private subsidiary of CytRx focused on transformational oncology drug development and diagnostics
▪ We have completed the pre-clinical phase for our ultra high potency LADRTM drug candidates and accompanying companion diagnostic
▪ Our four albumin binding drug candidates called LADRTM (linker activated drug release) have a unique albumin targeting and delivery mechanism that concentrates ultra high potency drugs inside the tumor, maximizing cell kill while minimizing systemic toxicity
▪ The potential to combine our targeted platform with immunotherapy represents a significant advancement in oncology treatment
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
2
Momentum has built for cytotoxins + immunotherapy in oncology
▪ Combining immunotherapy and cytotoxins is clearly becoming the 'wave of the future' for the treatment of cancer – the most successful immunotherapy products are leading these cytotoxic combination breakthroughs –
✓KEYTRUDA®, Merck & Co. Inc., ✓Tecentriq, Genentech/Roche and ✓Opdivo, Bristol Myers Squibb
▪ Immunotherapy and cytotoxin combinations represent a significant opportunity for the Centurion pipeline as our unique platform can significantly improve how cytotoxin therapy performs with immunotherapy
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
3
Immunotherapy and Cytotoxin Combinations Have Enormous Promise
Merck & Co. Inc, Keytruda. The Food and Drug Administration approved pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment of metastatic squamous non-small cell lung cancer.
Genentech/Roche: First positive Phase III study results for a cancer immunotherapy combination in breast cancer, with Tecentriq® plus nab-paclitaxel
Centurion’s ground-breaking innovation in cytotoxin therapy can improve efficacy even further with immunotherapy combinationsBristol Myers Squibb: Opdivo Plus Chemotherapy Showed Improved Progression-Free Survival Versus Chemotherapy in first-line advanced non-small cell lung cancer (NSCLC) with PD-L1 expression <1%, across squamous and non-squamous tumor histologies
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
4
Vision and Development Strategies
▪ Develop immunotherapy and LADRTM to work in combination in solid tumors
▪ Concentrate ultra high potency drug inside the tumor, maximizing tumor cell kill and minimize toxicity
▪ LADRTM has demonstrated broad utility across solid tumor types (lung, breast, ovarian, skin, head & neck)
▪ Our companion diagnostic (ACDx) is personalized medicine to identify tumors eligible for treatment with LADRTM
LADRTM (linker activated drug release) maximizes full potential to target and kill the tumor while minimizing systemic toxicity
Build tumor-agnostic development plan
Easily train oncologists on the
technology
Establish treatment globally
Attain blockbuster revenue
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
5
Centurion BioPharma Pipeline
LADR™ Albumin Binding Drug Conjugates
Preclinical Phase 1 Phase 2
Auristatin ProgramLADR-7: LADR-8:
Maytansinoid ProgramLADR-9:LADR-10:
Companion Diagnostic –ACDx (albumin companion dx) identifies patients across solid tumor types
▪ Four albumin binding ultra high potency LADR™ candidates ready for IND enabling studies
▪ Companion diagnostic – identifies patients to treat
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
6
LADRTM Platform Overview
2. Cleavable Linker• Novel linker keeps the
highly potent drug payload inactive until the conjugate reaches the tumor
• The linker is then cleaved which activates the payload
3. Targeting• Ensures rapid and
selective binding to circulating serum albumin
• Serum albumin transports the LADR™ drug to the tumor
1. Ultra High Potency Drug Payload
• Payloads are 10-1,000 times more potent than standard anti-cancer agents
• Similar to those used for ADCs (auristatins, maytansinoids)
Target albumin with ultra high potency drug in the tumor, minimize systemic toxicity
1 2 3
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
7
Albumin as a Targeting Delivery Vehicle
▪ Albumin
▪ Major source of essential amino acids (“fuel″) for cancer cells
▪ Localizes at tumor through the Enhanced Permeability and Retention Effect (EPR) effect and macropinocytosis
▪ Serves as a transport molecule for metabolites, hormones, and nutrients
▪ Long half-life (20 days)
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
8
LADR™ Mechanism of Action
Drug-linker conjugateis infused Tumor cells
Albumin transports drug to the tumor and
surrounding microenvironment
Linker dissolves in the acidic (low pH) environment and releases the drug payload
Rapid and specific binding to circulating albumin as the target
1
2
3
4
CytotoxicAgent Linker
CytotoxicAgent Linker
Albumin
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
9
LADRTM Drug Payloads -Auristatins
• Semi-synthetic derivatives of natural product dola-10
•Monomethylauristatin E (MMAE) used inclinically approvedADC Adcetris®
for treatmentof refractoryHodgkin lymphoma
Dolabella auricularia (Sea Hare)
LADR-7,8 are auristatinsLADR-7,8 are auristatins
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
10
LADRTM Drug Payloads -Maytansinoids
• Antimitotic agent by blocking polymerization of tubulin
•Derivative of maytansine (DM1) used inclinically approvedADC Kadcyla®
for treatmentof metastaticbreast cancer
Maytenus serrata(Ethiopian Shrub)
LADR-9, 10 are maytansines
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
(Roche/Genentech
11
Summary: preclinical LADRTM
data shows impressive efficacy
▪ Three poster presentations at AACR 2018
▪ Robust anti-tumor activity in multiple tumor types
▪ Durable responses averaged 60‒90 days
▪ Demonstrated statistically significant superiority over the control group and parent compound
▪ Highly effective even in large tumors with starting volumes of 270‒380 mm3
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
12
LADR-7,8 preclinical efficacy by tumor type
Tumor type Response rate
CR PR
NSCLC 78% 22%
Melanoma 76% 10%
Ovarian 45% 46%
H&N 0% 70%
LADR-7(Auristatin E)
LADR-8 (Auristatin E)
CR PR
NCSLC 19% 5%
Melanoma 29% 21%
Ovarian 40% 0%
Renal 29% 14%
H&N 40% 40%
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
13
LADR-9,10 preclinical efficacy by tumor type
LADR-9 (Maytansine)
LADR-10 (Maytansine)
Tumor Type Response Rate
CR PR
NCSLC 82% 12%
Breast 6% 65%
Ovarian 73% 9%
Renal 14% 0%
H&N 20% 60%
CR PR
NCSLC 45% 24%
Breast 0% 46%
Ovarian 43% 43%
Renal 0% 7%
H&N 10% 20%
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
14
LADRTM Targeting Tumorswith Albumin
Effective tumor targeting usingalbumin as a drug carrier
3. Improved tolerability allows for higher doses
2. Prolonged circulatory retention
1. Accumulation in tumor tissuedue to the EPR effect
(enhanced permeability and retention)
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
15
Companion Diagnostic: ACDx (albumin companion dx)
ACDx is an imaging test that identifies albumin uptake in tumors. By determining if albumin is in the tumor, we can
determine if treating with LADRTM (an albumin binding drug conjugate) is appropriate. This is personalized medicine that is
highly valued by oncologists.
What is ACDx?
How is ACDxused?
Uses Single Photon Emission Computed Tomography (SPECT), commonly used by oncology practices throughout the world. ACDx and LADR will be products sold to oncology practices.
GoalWhen positively screened with ACDx, we believe patients will have a very high response rate when treated with LADRTM.
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
16
ACDx will revolutionize the identification of solid tumors
OUR VISION:
Personalized Medicine with Solid Tumor-Agnostic Treatment
Identify eligible patients for treatment
Improve outcome of clinical trials
Improve probability of breakthrough
status and approval
Rationale for payer
reimbursement
Justification for premium pricing
ACDx creates value when working as a companion diagnostic with LADRTM
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
17
~40 min ~2 min
Preclinical SPECT/CT Imaging with 111In-C4-DTPA
Establish methodology in twohuman tumor xenograft models
Tumor type:
▪ LXFL 529 (NSCLC)
Study outline:
▪ Bilateral implantation
▪ TV ~100‒300 mm3 (left and right flank)
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
18
ACDx results in tumor-bearing nude mice
Representative 3D SPECT/CT image after 72 h
Distinct accumulation of albumin in the tumors
Kidneys are visible as the organs ofelimination
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
19
Centurion BioPharma Milestones
Event Completion Date
File one or more LADRTM patent applications Q4 2017
Initiate activities for GMP manufacturing of LADRTM linkers Q4 2017
Nominate one or more candidates for advancement into IND enabling studies
Q1 2018
Present preclinical data on LADRTM candidates at AACR ‘18 1H 2018
Begin LADRTM pharma partnering discussions 1H 2018
File patent application for companion diagnostic 3Q 2018
Closing of a strategic transaction 2019
Strategic transaction will determine next steps on pre-IND meetings, studies and filing
✓
✓
✓
✓
✓
✓ Represents a completed milestone
✓
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
20
Summary
▪ Goal – a Centurion BioPharma major strategic transaction to be closed in 2019
▪ Our four albumin binding drug candidates called LADRTM (linker activated drug release) have a unique targeting and delivery mechanism that concentrates ultra high potency drug inside the tumor, maximizing tumor cell kill and minimizing systemic toxicity
▪ Maximize full potential to target and kill the tumor, while minimizing systemic toxicity
▪ Novel LADRTM technology platform has additional applicability with immunotherapy
The World’s Leading Company Targeting
Albumin To Kill Solid Tumors
top related