cytrx (cytr) corporate presentation · ovarian 73% 9% renal 14% 0% h&n 20% 60% cr pr ncslc 45%...

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

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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



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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



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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



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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



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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



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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)



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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



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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



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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



(Roche/Genentech

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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



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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%



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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%



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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)



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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.



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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



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~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)



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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



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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

✓



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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



cytrx (cytr) corporate presentation · ovarian 73% 9% renal 14% 0% h&n 20% 60% cr pr ncslc 45%...

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