This document discusses an analytical methodology called RxOI2 that aims to de-risk investment decisions in early-stage drug development by predicting the likelihood of success for emerging drug targets. RxOI2 uses a weighted scoring system to evaluate scientific, commercial, and strategic factors for a target and predicts its true value proposition. It provides more reliable forecasts than other analytics that focus on later stages of drug development. The document outlines RxOI2's approach and provides an example case study analyzing targets for chronic hepatitis B.
Equivalence approches for complex generics DIA 11 april 2019 Bhaswat Chakraborty
This is a workshop that i gave a few days ago on bioequivalence of complex generics like peptides, polymers, liposomes, colloids, ophthamic and topical produtcts.
Fast track Designation is a designation for accelerated approval of drugs and medicines in US. Presentation contains brief view of this expedite program.
How can one regulatory program simultaneously benefit both blockbuster drugs and rare or neglected diseases? How can your company leverage the opportunities afforded by this program? This presentation walks you through the how’s and why’s of the FDA’s Priority Review Voucher program.
Equivalence approches for complex generics DIA 11 april 2019 Bhaswat Chakraborty
This is a workshop that i gave a few days ago on bioequivalence of complex generics like peptides, polymers, liposomes, colloids, ophthamic and topical produtcts.
Fast track Designation is a designation for accelerated approval of drugs and medicines in US. Presentation contains brief view of this expedite program.
How can one regulatory program simultaneously benefit both blockbuster drugs and rare or neglected diseases? How can your company leverage the opportunities afforded by this program? This presentation walks you through the how’s and why’s of the FDA’s Priority Review Voucher program.
Elizabeth Mansfield, PhD, discusses the FDA’s approach to regulation
of in vitro diagnostic tests.
Part of Dx2010, a workshop at MaRS focused on best practices and regulatory considerations for developing gene-based diagnostic and prognostic tests.
Decoding Phase II Clinical Trial Failuressubhabbasu
Clinical development is costly, with hundreds of millions of dollars spent to bring a drug to market. We identified the major reasons why Phase II clinical trials are terminated. Phase II serves as a major decision point, where a drug's effectiveness and safety are tested. However, our analysis of 444 clinical trials found Efficacy and Safety were reasons three and four, respectively, for trial terminations. Read to find out the top two reasons!
Is your product or medical device FDA-friendly? Learn about how to get a safe and effective product into the market, confronting risk management, complaints, and remediation services.
How early is too early for pharmaceutical market insights and product forecasts. A discussion on pipeline product research during early product development
Carlos Langezaal - Eisai Inc, Speaker at the marcus evans Discovery Summit Fall 2011, delivers his presentation on The Importance of Developing a Global Regulatory Strategy towards the Goal of Registration
Elizabeth Mansfield, PhD, discusses the FDA’s approach to regulation
of in vitro diagnostic tests.
Part of Dx2010, a workshop at MaRS focused on best practices and regulatory considerations for developing gene-based diagnostic and prognostic tests.
Decoding Phase II Clinical Trial Failuressubhabbasu
Clinical development is costly, with hundreds of millions of dollars spent to bring a drug to market. We identified the major reasons why Phase II clinical trials are terminated. Phase II serves as a major decision point, where a drug's effectiveness and safety are tested. However, our analysis of 444 clinical trials found Efficacy and Safety were reasons three and four, respectively, for trial terminations. Read to find out the top two reasons!
Is your product or medical device FDA-friendly? Learn about how to get a safe and effective product into the market, confronting risk management, complaints, and remediation services.
How early is too early for pharmaceutical market insights and product forecasts. A discussion on pipeline product research during early product development
Carlos Langezaal - Eisai Inc, Speaker at the marcus evans Discovery Summit Fall 2011, delivers his presentation on The Importance of Developing a Global Regulatory Strategy towards the Goal of Registration
A workshop presentation for Medical Affairs Strategic Summit West held in San Diego on September 23, 2019. The workshop covered the following learning objectives:
* Understand the factors involved in selecting and prioritizing indications
* Understand the importance of strategic market segmentation
* Understand how Medical Affairs can be involved in the process of new product planning
This presentation contains an overview of the scientific and business update provided by management during Critical Outcome Technologies' 2017 Annual General and Special Meeting of Shareholders on December 20, 2017.
Addressing the unpredictability issues in cancer vaccine trialsBhaswat Chakraborty
Determining the financial and decisional risks associated with the early phase trials
Understanding the best study designs and selection of controls to eliminate candidates
Understanding the end point selection for Cancer clinical trials
Comparing progress free and overall survival in Intend To Treat (ITT) and per protocol (PP) populations
Critically analysing the decision to proceed to Phase III or to terminate the trial
Case study: Discussing the best practice strategies on ‘Phase II clinical trials of vaccines – to go or not to go to Phase III
Exome Analysis with VS-CNV and VSClinical: Updated Strategies and Expanded Ca...Golden Helix
As exome sequencing continues to gain momentum as a comprehensive and affordable genetic test, many labs are considering the transition from their various targeted gene panels to a single comprehensive exome test. Along with the various challenges in small-variant analysis and interpretation of exomes, CNVs also require exome-specific considerations and strategies. In this webcast, we will review new capabilities and updated algorithms in the latest VarSeq release that will assist in any clinical exome sequencing workflow. Please join us in this webcast, as we review:
A new VS-CNV best-practice workflow with specialized features for calling CNVs on exomes and large panels with more precision, enhanced quality flags and additional outputs.
Enhanced analysis of variants found in exome sequencing, including non-coding clinically relevant RNA variants and mitochondrial variants
Additional CNV analysis capabilities such as CNV export and import as VCFs
The identification and interpretation of easily missed variants, such as those introducing novel splice-sites using the ACMG auto-classification and interpretation workflow
Strategies for incorporating disease-specific virtual gene panel lists into the filtering, quality and reporting capabilities of VSClinical
Exome sequence analysis is complex, and the process to define and validate a clinical exome test can be daunting. The VarSeq clinical suite has the flexibility and best practice workflows built-in to define and implement a repeatable and comprehensive workflow for CNVs detection and analysis by exome sequencing. We hope you can join this webinar to learn how to go from FASTQ to clinical reports for exome-based clinical tests.
Reviva Pharmaceuticals Holdings Inc is a clinical development pharmaceutical company. It is developing a portfolio of internally discovered therapies that address unmet medical needs in the areas of central nervous system, cardiovascular, metabolic and inflammatory diseases.
Can-Fite BioPharma Ltd. (NYSE American: CANF) is an advanced clinical stage drug development company with a platform technology that addresses multi-billion-dollar markets in the treatment of autoimmune inflammatory diseases including Psoriasis, and liver diseases including advanced liver cancer and NASH. Can-Fite’s drugs have an excellent safety profile with experience in over 1,000 patients. Can-Fite’s intellectual property portfolio consists of 13 patent families issued and pending. Piclidenoson and Namodenoson have been out-licensed in select territories with approximately $18 million received to date. Piclidenoson received approval for COVID-19 clinical trial in Israel in April 2020 and is expected to file its IND in the US in the near-term.
How and When to Kill a Program in New Product PlanningAnthony Russell
Presented at the 4th New Product Planning Summit in Boston (Dec 2 -3 , 2019). Presentation covers why weak programs should be cut from pharmaceutical and biotech pipelines, what defines a "weak" program, and describes objective methods to evaluate programs to help prioritize assets.
Mastering Regulatory Approval in New Orphan Drug MarketsLewis Lau
Presented at DIA 2015 Annual Meeting. A symposum titled "A Global Update on Orphan Drug" chaired by Mr Noriaki Murao
http://www.diaglobal.org/en-US/Flagship-Meetings/DIA-Annual-Meeting/Meeting-Program/Find-Sessions-and-Presentations/Event-Details.aspx?productID=3803687&eventType=Symposium&title=A%20Global%20Update%20on%20Orphan%20Drugs
This symposium addresses the current status and forthcoming activities related to orphan drugs in North America, EU and Japan. Orphan drug development is considered essential in these regions, and the various provisions to accelerate the development of orphan drugs have been implemented. However, some challenges still remain for the companies and the agencies wishing to pursue development and approval of orphan drugs in these regions.
Can-Fite BioPharma Ltd. (NYSE American: CANF) is an advanced clinical stage drug development company with a platform technology that addresses multi-billion-dollar markets in the treatment of autoimmune inflammatory diseases including Psoriasis, and liver diseases including advanced liver cancer and NASH. Can-Fite’s drugs have an excellent safety profile with experience in over 1,000 patients. Can-Fite’s intellectual property portfolio consists of 13 patent families issued and pending. Piclidenoson and Namodenoson have been out-licensed in select territories with approximately $18 million received to date. Piclidenoson received approval for COVID-19 clinical trial in Israel in April 2020 and is expected to file its IND in the US in the near-term.
Reviva is a Phase 3 clinical-stage biopharmaceutical company that discovers, develops and seeks to commercialize next-generation therapeutics for diseases representing unmet medical needs and burdens to society, patients, and their families. Reviva's current pipeline focuses on the central nervous system, respiratory and metabolic diseases. Reviva's pipeline currently has two drug candidates, RP5063 (Brilaroxazine) and RP1208. Both are new chemical entities discovered in-house. Reviva has been granted composition of matter patents for both RP5063 and R1208 in the United States (U.S.), Europe, and several other countries.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
1. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 1
De-Risking the Science for
Investment Decisions
2. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 2
Time, Cost and Compound Attrition
Preclude Early Entry and Late Exits
Source: PhRMA, the Pharmaceutical Research and Manufacturers of America
<0.01% of drugs in development will
ultimately make it to market
3. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 3
• Biopharma industry trend to early-stage deals
Identifying Early-Stage Assets for
Investment Decisions
Our target and therapy-specific methodology translates scientific,
commercial and strategic determinants into a single metric value proposition
to instantly identify early-stage targets with high likelihood of success
Evolution of S&D (search and develop) Big Pharma strategy
to identify external early-stage assets
Increased competition among Biotech Companies for
investor capital and in-licensing agreements (pipeline fill)
Investors increasingly interested in early-stage
targets/companies with IPO potential
• Currently available analytics focus on later-stage drug development and
are unreliable in forecasting success or risk at an early stage of drug
development
4. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 4
10%
30%
41%
IPOs for Preclinical and Phase 1 Assets
Shorten Time to Big Exits
IPOs by Stage 2012 2013 2014
Preclinical 1 1 8
Phase 1 0 8 18
Phase 2 3 12 26
Phase 3 6 8 6
Commercial 0 1 5
*Stage defined as last completed clinical trial.
Source: VentureSource, CB Insights, SEC Filings, and SVB proprietary data.
5. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 5
The Earlier the Asset, the More Stringent
the Analysis to Accurately Predict Success
Select
competitor
targets for
comparison
Assess
scientific and
clinical data
Predict
likelihood of
success
among
targets
Invest in the
early-stage,
market-leading
asset
Identify key
disease
target
Identify Select Assess Predict Decide
EFFORT
TIME
6. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 6
The RxOI2 Difference
Other Available Reports The RxOI2 Strategic Approach
Based on late-stage
clinical attributes
Mainly focused on late-stage
drug development
Forecasts based on historical averages;
not reflective of current market
Generalized; not customized
to target or therapy
Heavy reliance on stakeholder
opinions; not evidence-based
Static; boilerplate reports
Lengthy reports with non-relevant
fillers
Based on multiple determinants including
scientific, strategic and commercial attributes
Accounts for technical risk at an early stage
of drug development
Predicts the true value of innovative medicines
in the post-ACA health care paradigm
Dynamic scoring system with target- and
therapy-specific weighted attributes
Unbiased and quantitative
Validated methodology provides bold
conclusions on a target’s likelihood of success
Converts multiple dimensions of benefit and
risk into a single metric of value proposition
7. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 7
CHB Competitive Landscape
Rating Criteria
Scoring Process
Final Scores and Conclusions
Case Study: Predicting Likelihood of Success
of Emerging Targets in Chronic Hepatitis B
8. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 8
Rating Criteria Scoring Process Final Scores and ConclusionsCHB Competitive Landscape
Case Study: Predicting Likelihood of Success
of Emerging Targets in Chronic Hepatitis B
Relevant targets in preclinical,
phase 1, 2, 3 and launched
categories are researched
CHB COMPETITIVE LANDSCAPE
9. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 9
Case Study: Predicting Likelihood of Success
of Emerging Targets in Chronic Hepatitis B
Rating Criteria Scoring Process Final Scores and ConclusionsCHB Competitive Landscape
Therapy-specific rating criteria
and weighted attributes are
determined
RATING CRITERIA
10. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 1 0
Rating CriteriaCHB Competitive Landscape Scoring Process Final Scores and Conclusions
Each compound is
extensively
researched
SCORING PROCESS
Case Study: Predicting Likelihood of Success of
Emerging Targets in Chronic Hepatitis B (cont’d)
Data applicable to
target-specific scoring
of the various
attributes are
captured and
evaluated
11. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 1 1
Case Study: Predicting Likelihood of Success of
Emerging Targets in Chronic Hepatitis B (cont’d)
Rating CriteriaCHB Competitive Landscape Scoring Process Final Scores and Conclusions
Final scores for emerging
drugs in preclinical or
phase 1, 2, or 3 stages
are calculated using our
therapeutic area-specific
methodology
FINAL SCORES AND CONCLUSIONS
12. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 1 2
RxOI2 in Action: Clonidine, Birinapant
and EBI-005
Recent Drug
Development Failures
RxOI2
Critical Findings
Impact on the
RxOI2 Value Proposition
BioDelivery Sciences’
clonidine topical gel fails
phase 3 study for painful
diabetic neuropathy
Mar 30, 2015
• Analgesic effect of clonidine
analgesic effect is dependent on the
presence of functional capsaicin-
responsive nociceptors in the skin
(phase 2)
• Biomarkers (Efficacy and Safety):
The clonidine phase 3 study did not
include the functional biomarker,
lowering the scoring metric for
success in the pivotal trial
TetraLogic halts phase I study
of birinapant in chronic
hepatitis B because of safety
concerns of cranial nerve
palsy
May 6, 2015
• Safety signal (Bell’s palsy--, a
dysfunction of the cranial nerve )
reported with high dose of birinapant
(phase 1*)
• Rare instances of Bell’s palsy and
other cranial nerve involvement in
hepatitis E infections and as a
complication of hepatitis B
vaccination (published literature)
• Earliest Clinical Data and Disease
Research: High dose safety concerns
in cancer patients and predisposition
of CHB patients to cranial nerve
palsy lowered the scoring metric for
success in CHB
Eleven Biotherapeutics’
EBI-005 fails phase 3 study in
patients with dry eye disease
(DED)
May 18, 2015
• Lack of statistically significant
difference in clinical effects of
EBI-005 in patients with DED
(phase1b/2)
• False-discovery Rate: Lack of
statistical significance in earlier trials
lowered the scoring metric for
success in pivotal, large-scale phase
3 study
*A phase I study using single agent birinapant in patients with relapsed myelodysplastic syndrome and acute myelogenous leukemia.
13. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 1 3
Our Methodology is Validated in the Most
Active Areas of New Drug Development
NumberofProductsinDevelopment*
Medicines in Development (2013–2014)
*Some medicines are being explored in more than one therapeutic category.
SOURCE: Pharmaceutical Research and Manufacturers of America. "Medicines in Development:
Biologics—Overview." Washington, DC: PhRMA; 2013.
14. R X O I 2 │ C O N F I D E N T I A L │ S L I D E 1 4
The RxOI2 Difference:
De-Risking the Science of Drug Development
UNIQUE
methodology
We consider what the data mean in the context
of the disease and the competitive environment
SPECIFIC
evidence
We utilize our expertise in a broad range of
therapeutic areas to synthesize evidence
specific to the disease category
data
ANALYSIS
We leverage our unbiased analyses
on science-driven data, not trends
or opinions
We use our proprietary
methodology to make
scientifically validated
recommendations
BOLD
conclusions
Editor's Notes
At RXOI2, we predict the true value of innovation by translating scientific, strategic, and commercial considerations into a single metric of value proposition for drugs in early-stage development. Our validated methodology provides bold conclusions that inform actionable drug development, acquisition and investment ideas.
With less than 0.01% of all drugs in development actually making it to market, an early-stage, asset-centric approach to development and investment has taken center stage in the past several years.
Source: http://www.phrma.org/sites/default/files/159/rd_brochure_022307.pdf
The preponderance of early-stage deals reflects the fact that value is greatest if alliances are formed early in a drug’s life. In 2014, $355 billion in total transactions, including $53 billion in partnering deals, $16.5 billion in venture investments, and more than 63 IPOs were reflected in these data. The RxOI2 early-stage target and therapy-specific methodology de-risks the science with deep due diligence that translates into a single metric value proposition to identify early-stage targets with a high likelihood of success.
http://www.forbes.com/sites/davidshaywitz/2015/03/07/high-acquisition-premiums-and-many-layoffs-predictable-consequences-of-externalizing-pharma-rd/
http://www.biotech-now.org/business-and-investments/2014/06/therapeutic-licensing-and-ma-deals
Last year, early-stage biopharma companies accounted for a larger share of the IPO market, with pre-clinical or phase 1 assets comprising 41 percent of those transactions. Biopharma companies under increasing competition for early stage funding, are scrutinized more heavily and asked to prove that their ‘hope’ will translate into value. Additionally, only a small number of health care investors are consistently successful in early stage exits. However, neither biopharma nor early-stage investors have been able to consistently de-risk the science, particularly with early-stage assets.
Source: http://www.svb.com/News/Company-News/A-Year-of-Dazzling-Returns--2014-Healthcare-Investments-and-Exits/?site=uk (page2)
A more stringent and structured scientific analysis of the early-stage drug profile is required to predict success for clinical development and investment. RxOI2 has developed a validated methodology to accurately predict the science of success in early-stage drug development
The RxOI2 methodology accounts for technical risk at an early clinical development stage by using a dynamic scoring system with target- and therapy-specific weighted attributes. We research and analyze more than 20 dimensions of scientific and clinical data into a single, comparative metric of value proposition.
We compile and score the data for each target in 6 key areas: (1) target validation and proof of mechanism, (2) target engagement and proof of principle, (3) proof of concept, (4) therapy characteristics, (5) stakeholder opinions, and (6) benchmarking metrics.
All drug targets in preclinical, phase 1, 2, 3 and post-approval in a particular therapeutic area are thoroughly researched. In many therapeutic areas of active development, there are large numbers of compounds to be considered. In this example case, we considered 38 compounds for CHB. Our Alzheimer’s algorithm considers 200 compounds in early-stage clinical development.
Utilizing the validated core set of attributes, individual characteristics of each target are scored and calculations based on a therapeutic area-specific attribute weighting system result in a final score for each compound.
Minimum scores for likelihood of success are established based on retrospective validation of both approved and terminated drugs, with predictive cutoff scores specific to the therapeutic area. A comprehensive report with hierarchical metrics and conclusions based on our validated methodology is generated.
Conclusive value proposition metrics are applied to predict which drugs are most or least likely to advance to the next stage of clinical development, and to an overall end goal of post-marketing approval.
RxOI2 prospectively predicted the recent failures of clonidine, birinapant and EBI-005. Our methodology routinely includes an analysis of efficacy and safety biomarkers for patient selection, a comprehensive review of all clinically available data across every therapeutic use for evaluated drugs, exhaustive disease research, and statistical considerations such as false-discovery rates in phase 1b/2 clinical studies.
RxOI2 analytics can be conducted and reported on assets in the most active areas of therapeutic development. In many of these cases, we have the method validated, allowing us to provide clients with full reporting in about 4 weeks.
Source:
http://www.phrma.org/sites/default/files/pdf/2014_PhRMA_PROFILE.pdf (Figure 13)
http://www.phrma.org/sites/default/files/pdf/2014-cancer-report.pdf
http://www.phrma.org/sites/default/files/pdf/MedsInDevInfectiousDiseases2013.pdf
http://www.phrma.org/sites/default/files/pdf/MedicinesInDevelopmentNeurologicalDisorders2013.pdf
http://www.phrma.org/sites/default/files/pdf/LeukemiaLymphoma2013.pdf
http://www.phrma.org/sites/default/files/pdf/Rare_Diseases_2013.pdf
http://www.phrma.org/sites/default/files/pdf/diabetes2014.pdf
http://www.phrma.org/sites/default/files/pdf/2014-meds-in-dev-arthritis.pdf%27s%202013.pdf
Our unique methodology is based on specific scientific and clinical evidence. We utilize this extensive research to analyze the data in a specific therapeutic area and arrive at validated conclusions for drug development and investment.