we develop oncology drugs · metastases to the brain. company presentation august 2017. 9 ... use...

We Develop Oncology Drugs with Precision

Company Presentation August 2017 1

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• Monthly costs of newly approved Cancer drugs are

now >10.000 USD per patient

• Products for hard to treat cancers may be approved

with 20-30% response rate

• But only 2½ % of products in development get

approval

• Very often safety is ok and some patients benefit - but not enough to warrant approval

• No technology as broadly applicable and useful in ‘non-targeted drugs’ to find the patients who will

benefit until now

Some Patients benefit from a drug – others do not

The FDA estimates that only 25% of hard to treat cancer patients receives an effective medical treatment

Company Presentation August 2017

https://www.fda.gov/downloads/scienceresearch/specialtopics/personalizedmedicine/ucm372421.pdf

https://www.fda.gov/downloads/scienceresearch/specialtopics/personalizedmedicine/ucm372421.pdf

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Digital Precision Gene Expression Pharmaco-omics - a Validated Drug Response Predictor Platform

Drug Response Prediction DRP™

Oncology Venture uses the DRP™ technology to analyze individual patients tumors for gene patterns that show whether the patients will benefit from the drug or not


DRP™ & Understanding Complexity

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How APO010 - a TNF product - works

The traditional biomarker approach is identifying one single mutation that can be targeted by a drug. An example is the drug, Herceptin that targets the HER2 gene which is high expressed by about 25% of all breast cancer patients. Still only approximately20% of these respond in spite of amplification of the gene.


The DRP™ builds on systems biology. Below to the left the traditional, understanding of how a TNF product works e.g. APO010. To the right is a map over TNF effect that shows > 680 protein-protein interactions are in play when administering a TNF targeting product. This clearly indicates that the traditional understanding is too simplified to understand how the cancer operates and how e.g. APO010 works.

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To run the individual DRP™ analysis on the patients we

need messenger RNA (mRNA) data from the

patients biopsy. Biopsies from the time of the

diagnosis can be used . The lab work can be done in 72

hours.

Cancer Cell line drug data are linked to genes (mRNA) and the relevance of individual genes sorted out.

6Company Presentation August 2017

A conventional Affymetrix chip is used to obtain the complete gene expression messenger RNA (mRNA) from the patient’s biopsy.

The million of data points from the chip is fed into the algorithm – and the DRP analysis on the individual patient analysis begins.

One step to obtain the Complete gene expression= mRNA

1 million data points 25.000 genes for each human cell line and for each individual patient

For more technical information please see appendix in this presentation.

SHORTEN Development Time

INCREASE Probability of Success REDUCE Capital Investment

INCREASE Sales

Understanding complexity to gain Precision


Our Product Pipeline

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Focused on EFFICACY CANCER INDICATION SCREENING PHASE 2 RANDOMIZED PHASE 3 OR PIVOTAL

Metastatic Breast

Metastatic Breast (Cadila)

Prostate (Cadila)

Head & Neck (Cadila)

Esophagus (Cadila)

Skin (Cadila)

CANCER INDICATION SCREENING PHASE 2 RANDOMIZED PHASE 3 OR PIVOTAL

Prostate

Ovarian

Liver

CANCER INDICATION SCREENING PHASE 2 RANDOMIZED PHASE 3 OR PIVOTAL

Multiple Myeloma

Metastatic Breast

We have an exiting and diversified anti cancer pipeline portfolio of new targeted drugs like the PARPifrom EISAI and ImmunoOncology drug APO010.

We have two cutting edge liposomal formulations –one LiPlaCis has a targeted and proven release of cisplatin directly at tumor site – and 2X-111 (see next slide) crosses the Blood Brain Barrier to allow treatment of tumor or metastases to the brain.


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Product Indication SCREENING PHASE 2 RANDOMIZED PHASE 3 OR

PIVOTAL

2X-111 TOP2# liposomal-GSH

Metastatic Breast

2X-111 TOP2# Liposomal-GSH

Brain tumors (Glioblastoma)

2X- 121 PARP# Metastatic Breast

2X-131 TOP1# Under negotiation

Ovarian Cancer

OV-SPV 2

Tyrosine kinase # SCREENING PHASE 2 RANDOMIZED PHASE 3 OR PIVOTAL

Renal cancer DRP test in data from Phase 3 trial

Liver cancer DRP test in data from randomized Phase 2 trial

2X Oncology Inc. is currently 92% owned by OV

OV-SPV2 Aps is currently owned by 40% by OV and 10% by MPI

New targeted drugs with Proven efficacy in need for a DRP focus to precision:Irofulven has been in 1600 patients with effect in prostate, ovarian and liver cancer.2X-131 a TOP1 # is in negotiation has a favorable tox profile and efficacy data.TKI from Novartis with promising Phase 3 data and data on 160 to be tested by our DRP™.

Product Pipeline cont..



LiPlaCis image of success in patient with skin cancerSquamous cell carcinoma patient

A 66-year old male with Squamous cell carcinoma who has failed 2 prior lines of chemotherapy.

Partial Response (PR) after 8 weeks of LiPlaCis® treatment, during 9 weeks treatment period.

He was then eligible for plastic surgery. After 12 month the patient was still in complete remission.

Result after 5 cycles of LiPlaCis® treatment

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LiPlaCis image of success – Patient with gastric cancer


>1200

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Intelligent Targeted Cisplatin

• Lipid-based, nano-encapsuled formulation preciselydelivers cisplatin at tumor site

• Now including patients selected via DRP™ in phase 2study

• Activity seen in Breast, Esophagus, Skin and ColonCancer

• Partnership with Cadila: four phase 2 studies, onephase 3 study

• Market for Breast Cancer treatment ~ 8 billion USD2014, expected to reach 18 billion USD by 2022

Complemented by LiPlaCis DRP™ for patient population enrichment


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Immuno-Oncology Drug with Unique Mechanism of Action

• Imitates T-cells, inducing apoptosis of malignant cells

• Screening Multiple Myeloma (MM) patients for Phase 2

• Focused phase 1b/2 trial at 3 sites ongoing recruitingMM patients in Denmark

• Big demand for MM treatment: market value 2014 over7 billion USD

• Cancer immunotherapy drug market estimated to35 billion USD by 2023

Complemented by APO010 DRP™ for patient population enrichment

APO010 Mechanism of Action


Great in some patients

- and we willfind them


Irofulven has demonstrated a 10% response rate in Prostate cancer previously treated with docetaxel and a 12% response rate in ovarian cancer previously treated and relapsed after standard chemotherapy with paclitaxel and carboplatin

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Tested in Over 1300 Patients - Effective for Several Indications

• Semi-synthetic drug, originating from natural productisolated from fungus Omphalotus Illudens

• Exerts anti-tumor activity by producing DNA adductsthat can only be repaired by the TC-NER pathway

• Screening patients ongoing to be included in focusedphase 2 multi-center trial in SE & DK

• Market for Prostate Cancer drugs expected to triplefrom 2,5 billion USD 2013 to 7,6 billion in 2022

• Average treatment cost USD 40´/patient --> significantpotential for Irofulven

Complemented by Irofulven DRP™ for patient population enrichment


Data from 3.000 patients. Each patient is a green circle.

2X-111: Glutathione-enhanced PEGylated Liposomal Doxorubicin

• Glutathione (GSH) – enhancement of

PEGylated liposome exploits the GSH transport

pump in the Blood Brain Barrie (BBB) to allow

transfer of 2X-111 into the brain

• IP includes GSH-PEGylated liposome delivery

system in combination with anthracyclines

Novel Trans-BBB Drug Candidate

glutathione

PEG

doxorubicin

liposome

• Validated DRP – please see slide 20

• U.S. IND obtained June 2017

• Drug product manufacturing underway

• DRP™ established for 2X-111 & validated for

use in planned studies

• Danish registry of breast cancer population

(~1,200 patients) available for Phase 2 study

• Glioblastoma patients to be screened with 2X-

111 DRP™ CDx at Copenhagen and Duke

University Hospitals

Current Status


2X-121: PARP 1/2 and Tankyrase 1/2 Inhibitor

• Tankyrase 1/2

• Important regulators of canonical Wnt/β-catenin, a critical checkpoint in metastases, particularly in triple-negative breast cancer

• Established efficacy & safety profile• No myelotoxicity

• Drug product manufactured

• DRP™ established for 2X-111 & validated for use in

genetic data from 13 patients from a Phase 1 study

• Danish registry of breast cancer population (~1,200

patients) available for Phase 2 study

Status from previous Phase 1*• Well tolerated

• 46% disease control

• 7.1% partial responses in all comers

• 2 durable partial responses, 200+ days

* Without DRP™

Current StatusOrally bioavailable, brain penetrable, small molecule drug

Potent inhibitor of• Poly(ADPribose)

polymerase (PARP)1

• A key molecule in sensing

and repairing single strand

DNA breaks

• PARP2: additional repair

mechanism


2X-121: PARP 1/2 and Tankyrase 1/2 Inhibitor

Clinical Opportunities with validated DRP™ CDx – please see slide 20

Other DRP™ and Wnt pathways

Other homologous Recombination deficient

BRCA1+2 mutated

Likely non-responders to 2X-121

High likelihood sensitive subgroups are identified by the 2X-121 DRP™

Metastatic breast cancer Brain metastases from breast cancerOvarian cancerEndometrial cancer Prostate cancer

Dual inhibitory action of 2X-121 against PARP 1/2 and Tankyrase 1/2 provides

broader activity than current PARP inhibitors

Lack of transport by P-glycoprotein potentially overcomes resistance to current PARP inhibitors


2X-131: Topoisomerase 1 Inhibitor – under negotiation

• MOA: cytotoxicity from double strand DNA damage

produced during DNA synthesis

• Favorable safety profile

• Clinically-demonstrated efficacy in wide range of cancers

• Drug product manufactured

• DRP™ established for 2X-111 & validated for use in 13

biopsies from Phase 1 study

• Danish registry of breast cancer population (~1,200

patients) available for Phase 2 study

Status from previous Phase 1*• Well tolerated

• 46% disease control

• 7.1% partial responses in all comers

• 2 durable partial responses, 200+ days

* Without DRP™

Current StatusOrally bioavailable, small molecule drug

• Orally bioavailable small

molecule camptothecin

• Binds to the

topoisomerase 1-DNA

complex

• Prevents re-ligation of

single strand breaks that

are induced by

topoisomerase 1 to relieve

torsional strain in DNA


DR

P™

Usa

ge E

xam

ple

s

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Predicting Who Should Have: 5FU, liposomal cisplatin/LiPlaCis®, 2X-121/PARPi and liposomal doxorubicin/2X-111

Survival without chemotherapy.Data published in PlosOne May 2016

Colon Cancer Survival doubled

Bottom 50%

Top 10% p = 0.05 HR = Inf

Top 20% p = 0.08 HR = 2.5

Top 50% p = 0.08 HR = 1.9

DRP shows 6 modifference in sensitive and non-sensitive metastatic Breast Cancer patients treated with doxorubicin. Data published at ASCO 2017

Data from 13 phase 1 patients with solid tumors analyzed and split into two groups. The DRP can with a p-value of 0.7 identify responders from non-responders to the PARPi2X-121 (E7449). Internal report. Press release Aug. 1st 2017

DRP can identify the TOP 10% of NSCLC patients that were cured by surgery and adjuvant cisplatin treatment. The bottom 50% had no advantage of cisplatin treatment. Data published at ESMO Oct. 2016

P-values shown are for the logrank test. The more sensitive Cox proportional hazards regression gives a univariate p=0.007 and a multivariate(Including age, stage & histo) p=0.013

Phase 1 13 patients


For all drugs Scalable Patient selection with DRP™

POC study to include most likely responders in trial to demonstrate DRP strength

The clinical and commercial opportunity is often much bigger than the PoC.-> Either treat more sensitive patients

- Or avoid treating the refractory patients


SHORTEN Development Time

INCREASE Probability of Success REDUCE Capital Investment

INCREASE Sales

Understanding complexity to gain Precision

OV Business Facts

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• Oncology Venture was formed in 2012 by Danish and US oncology specialists, as aspin-off to Medical Prognosis Institute (MPI.ST)

• Listed as Oncology Venture AB , Stockholm, Sweden on July, 2015 (OV.ST)

• Initial tock share rate: SEK 7.40

• Number of shares 10,877,007

• Stock share rate per August 1, 2017: SEK 30.5

• Raised a total of 10million USD at 7.40 SEK, 10.00 SEK, 29.00 SEK and 42.00 SEK

• Market value per August 1, 2017: 332 mSEK /41 mUSD


Recent Achievements✓ OV enters development deal with Cadila Pharmaceuticals on LiPlaCis® and its DRP™ value 20 million USD

✓ LiPlaCis™ - First DRP-positive Breast Cancer patient obtained significant reduction of tumor

✓ Prediction of Cisplatin and Vinorelbine sensitivity in Lung Cancer published

✓ Prediction of 5FU sensitivity in Colon Cancer published

✓ Prediction of Epirubicin, Fulvestrant and aromatase blockers Exemestane and Anastrozole in 800 breast cancer patients

✓ Technology acknowledged by Experts – 2 Eurostars Grants and 1 Medicon valley/Boston Grant totaling 38 million SEK

✓ 10 Danish centers are screening breast cancer patients for LiPlaCis and umbrella studies

✓ Four Danish centers have started screening Multiple Myeloma patients for OV's APO010 Study

✓ One Swedish and Two Danish sites open in the Screening Study of Prostate Cancer patients for Irofulven

✓ OV incorporates 2X Inc, a US company focusing on women's cancers Raised 3½ million USD in January 2017

✓ OV incorporates OV-SPV2 a raised 0.5 million USD January 2017

✓ OV global DRP™ exclusivity for 3 years from MPI (December 31, 2019)

✓ APO010 DRP focused phase 2 in multiple myeloma started

✓ Epirubicin DRP at ASCO, LiPlaCis first data on DRP and Efficacy

✓ Eisai deal, 2B3-101/PARPi deal

✓ Novartis deal, Phase 3 TKI24Company Presentation August 2017

Let’s Talk!

ULLA Hald Buhl

Oncology Venture

Chief Operating Officer

Founder

PETER Buhl Jensen

Oncology Venture

CEO

Founder

NIKOLAJ Buhl Jensen

Oncology Venture

Chief Financial Officer

Appendix


DRP™ Validated in Nearly 40 Clinical Trials

• Epirubicin in metastatic breast cancer http://abstracts.asco.org/199/AbstView_199_192238.html

• Epirubicin in breast cancer; ABVD in Mb.Hodgkin; methotrexate in childhood ALL https://academic.oup.com/jnci/article/105/17/1284/908746/Independent-Validation-of-a-Model-Using-Cell-Line

• Epirubicin, Exemestan, Anastrozole, and Fulvestrant in advanced breast cancerhttp://www.medical-prognosis.com/investor-and-media/20170124-drp-successfully-predicts-effect-of-4-breast-cancer-drugs-for-personalized-medicine/?origin=announcements

• Gastroesophaeal Cisplatin, Epirubicin and Capecitabinehttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148070

• Adjuvant 5FU in colon cancer http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0155123

• Belinostat in AML http://www.oncologyventure.com/wp-content/uploads/2016/04/Bullinger_ESMO2012.pdf

• Adjuvant Cisplatin and Vinorelbine in NSCLC http://oncologypro.esmo.org/Meeting-Resources/ESMO-2016/Multigene-expression-profile-for-predicting-efficacy-of-cisplatin-and-vinorelbine-in-non-small-cell-lung-cancer

• Fulvestrant in breast cancer http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087415

• CHOP and CHOEP in lymphomas https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333339/



Mathematical algorithm developed using a validated, scalable statistic tool that is highly extensible.

The DRP is scalable and includes machine learning.

Our DRP™ separates responders versus non-respondersPatient data makes the model clinically relevant

In vitro Model

0 20 40 60 80 100

0.00

0.01

0.02

0.03

0.04

0.05

Prediction score

Den

sity

responders (CR+PR)

nonresponders (SD+PD)

P=0.11

P=0.11

Clinical Relevance FilterMPI/OV Proprietary Rights

0 20 40 60 80 100

0.00

0.01

0.02

0.03

0.04

0.05

Prediction score

Den

sity

responders (CR+PR)


P=0.01

Meta analysis of 3255 human samples used for model refinement (filtering)

P=0.01

Utility in ClinicMPI/OV Proprietary Rights

0 20 40 60 80 100

0.00

0.01

0.02

0.03

0.04

0.05

Prediction score

Den

sity

responders (CR+PR)


P=0.003

Meta analysis of 3582 tumors used for covariate modeling, clinical validation, comparison between 27 cancer typesP=0.003

Drug Specific

DRP™ Biomarkers

Individual drug sensitivity/ resistance and gene expression correlations in various human cancer cells grown in the lab


>10% ownership in OV

MPI will receive a 10% ownership share in 2X Oncology after ongoing series A round.MPI have a 20% ownership share in OV-SPV2 which will be 10% after next financing round.

40% ownership*92% ownership

Drugs:LiPlaCisAPO010Irofulven

Drugs:2X-1112X-1212X-131

Drug:BigP TKI

OncologyVenture

Medical PrognosisInstitute

OV-SPV2**2X

Oncology

* Will be diluted after investment round** OV has a 5 million USD share buy-back option to increase to 90% of ownership

Shareholding in MPI, OV, 2X and OV-SPV2

>10% ownership


we develop oncology drugs · metastases to the brain. company presentation august 2017. 9 ... use...

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