Key Activities Ofer Reizes, Ph.D. Skills Development Director 1 - - PowerPoint PPT Presentation

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Key Activities

Ofer Reizes, Ph.D. Skills Development Director

Key Activities

Core Question: What key activities required for your Value Propositions?

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Critical Activities

• File the strongest possible IP
• Generate data
• Bench, pre-clinical, and clinical
• Conduct a clinical trial
• Sensitivity and Selectivity studies
• Obtain regulatory approval
• Obtain reimbursement
• Conduct a cost outcomes study

We Know Pathways

Translational Research is more than “Bench to Bedside”

Navigating the Ecosystem of Translational Science Understanding your ecosystem is critical for your activities

Pre- Clinical Clinical Trials KOLs CROs Efficacy Toxicology Regulatory Pathway CROs FDA IP Physician/ Hospital Reimbursement Patient Dosing Side Effects Compliance Cure/Treat

Generic Therapeutics Ecosystem

Target ID Validation Pre-clinical Studies Lead Optimization Lead ID First in man

HTS Medicinal Chemistry Efficacy Studies Pharmaco- kinetics In vitro Toxicology In vivo Toxicology ADME

Therapeutics Discovery Activities

Two Species Efficacy Studies Large Animal Toxicology Pre-IND

Devices Activities Design Controls Waterfall

The Critical Three Elements

Technological Solution Intellectual Property

How does this fit within the ecosystem?

Compelling Clinical Need Intellectual Property

MVP

Technological Solution

Minimum Viable Product

• Generate prototype to demonstrate problem-solution relationship.
• Articulated a problem definition based on your understanding/experience
• Provide High-Level Engineering Specifications
• Understand the minimum feature list to
• Prototype  Customer Segment  Value Proposition  Prototype.
• Bench testing to demonstrate solution
• Simulation to aid engineering specifications (e.g. stent design, fatigue testing,…)
• Pre-Clinical model for safety and efficacy (acute & chronic models)
• Generate data to substantiate your claim and test hypothesis.
• What are you trying to prove?
• To whom are you trying to prove it? (customer, VC, FDA or regulatory body)
• Think feasibility ($) versus statistical significance ($$$)

Goal of MVP Prototype

• “Show-n-Tell” to your stakeholder and help envision product

features and discuss product-market fit.

• Articulate the main idea and could point-out to design risks.

This is important for Reg. activity of dFMEA for instance.

• Helps you in choosing your product features and iterate

prototype to determine the minimum features needed and not dilute your value proposition.

• Question = What should your M.V.P prototype look like?

Clinical Activities for Therapeutics/Devices

How do these activities fit within YOUR ecosystem? Who will you partner with? Do you have a timeline?

Pre- Clinical Clinical Trials Regulator y Pathway KOLs CROs CROs FDA Efficacy Toxicolog y IP

Pre-clinical Models – Can you show…

• Disease modifying mechanism of action.
• Benchmark against competing programs.
• You are competing against everything including generics and pre-

clinical programs.

• Generate and evaluate.
• Highest quality therapeutics or optimal design of your device.
• Metrics need to be understood from day one and constantly reviewed.
• Your expertise must be the best in the world.
• What does it cost? Who cares the most? What will they pay?

Clinical Trials are a Critical Activity

Activities Dictate your Timelines

Know YOUR Competition

Tools & Platforms Pharma & Biotech Cybel e

Know YOUR Partners

Activities and Risk

• Financing Risk is THE major hurdle to success.
• IP underpins your exit value.
• Regulatory Pathway and Reimbursement define the size and

scope of the required clinical trial and finance ability.

• The clinical trial is the ultimate test of the hypotheses.

Intellectual Property - Activities

• Seek a professional opinion.
• The quality of your Intellectual Property underpins Exit Value.
• Quality of IP is evaluated on some of these criteria:
• Novel, non-obvious, Utile  Do you have a patent?
• Freedom-to-Operate  Are you borrowing someone else’s IP to build yours?
• Blocking IP  Are you preventing competitors from practicing in this field?
• Core patents can often be augmented with strong follow-on
• patents. The process of iterating and refining leads to better IP.

Clinical Needs Are Usually Addressable By Multiple Technologies

Don’t chase clinical needs with technology.

• Be technology agnostic  FOCUS ON THE NEED
• Gravitate towards the technical solution with the broadest and deepest

IP protection.

• A better clinical solution with weaker patent coverage will have a harder

time being commercialized than a less than ideal clinical solution with stronger patent protection (will discuss further with IP workshop).

Other Types of Intellectual Property

• Trademark:
• Protect branding and marks.
• Stronger if registered.
• Trade Secret:
• No IP filed, but you have to demonstrate

you have restricted access.

• Patent:
• Government Monopoly.
• Strongest Barrier to Entry.

It ALWAYS Comes Back to Knowing YOUR Ecosystem (Pathway)

Regulatory Activities

Pre- Clinical Clinical Trials KOLs CROs Efficacy Toxicology Regulatory Pathway CROs FDA IP Physician/ Hospital Reimbursement Patient Dosing Side Effects Compliance Cure/Treat

Generic Therapeutics Ecosystem

Early Determination of Regulatory Pathway is Critical

• 75% of all money raised will be spent on clinical studies and

regulatory approvals.

• Major factor in getting financed.
• Major factor in Product Market Fit and strategy.
• Customer Discovery and Interviews can help.
• Identify the data set necessary to show that your invention does or does

not deliver the hypothetical value in humans.

• Identify clinical trial design options.
• Regulatory approval often involves the opposite of IP goals 

similarity to existing approaches versus novelty.

• Identify path of least resistance in getting regulatory approval.

Therapeutics Need to Generate Scientific Evidence (Data)

• The system for ranking the quality of clinical evidence is

known as “Evidence-based Medicine.”

• Demonstrating Safety and Efficacy of therapeutic requires

hard data with clear endpoints.

• The highest level of evidence (and most expensive) is a

prospective, randomized, placebo-controlled, double blind trial (RCT) published in a peer review journal.

• The value of your company and technology will be bracketed

by the strength and clarity of your data.

• Major risk to getting funding: Equivocal Data

Typical development program

Nonclinical

Animal data usually surrounding safety but efficacy might be added in POC

Clinical

Phase I Usually safety, SAD, MAD, PK/PD, very short term Phase II Efficacy signal studied, dose ranging, may include PK/PD Longer than in phase I, some safety data accumulated Phase III More robust, larger numbers, and longer duration, would serve as pivotal trials for approval

NDA/BLA

* POC proof of concept; SAD single ascending dose; MAD multiple ascending doses; PK pharmacokinetic; PD pharmacodynamic; NDA New Drug Application; BLA= Biologic Licensing Application

New Drug Application review (focus)

• Substantial evidence of effectiveness

“. . . Evidence consisting of adequate and well controlled investigations, including clinical investigations, by qualified scientific experts, that proves the drug will have The effect claimed by its labeling. . .” (Kefauver-Harris Drug Amendments to Section 505[d] of Federal Food, Drug and Cosmetic Act, 1962)

• Safety (Federal Food, Drug and Cosmetic Act of 1938)
• Labeling (Original Food & Drug Act of 1906)

So will anyone pay for your technology?

Why Reimbursement is Important for devices?

• Seek professional opinion  Very dynamic field. INTERVIEW.
• Reimbursement is the driver of revenue and profitability of medical

device start-ups and typically.

• No existing coverage/code = Hard to finance (must be disruptive technology)
• Near Term suboptimal code that might be changed over time with compelling

data demonstrating superior clinical efficacy = Good chance to finance.

• Reimbursement for public payors is determined by CMS (Center

for Medicare and Medicaid Services), private payors tend to follow CMS’s lead, but occasionally do not.

• New reimbursement code = 2-3 years post FDA approval.

Reimbursement is Required to Effectively Sell Therapeutics

• Major concern for VCs and other financers.
• No existing coverage/code = unfinanceable
• Reimbursement for public payers is determined by CMS

(Centers for Medicare and Medicaid Services).

• Obtaining a new reimbursement code can take 2-3 years

AFTER getting FDA regulatory approval.

Reimbursement = Coverage, Coding, Payment

Coverage: The terms and conditions under which Medicare or private payers will or will not provide payment.

• Dependent on scientific evidence and data generated by comparative clinical

trials and published in peer reviewed journals.

• The evidence must support effectiveness in substantially improving health
• utcomes over existing therapies.
• Therapeutic must demonstrate “medical benefit” and “added value.”

Reimbursement = Coverage, Coding, Payment

Codes link coverage to payment. Coding consists of:

• CPT (Current Procedural Terminology) Codes identify medical

procedures performed by physicians.

• ICD-9 (International Classification of Diseases, 9th Revision) Codes

convey a patient’s diagnosis(es) and provide the medical justification for the episode of care for which the provider is filing a claim.

• They are used in both the inpatient and outpatient settings.

– ICD 10 is coming out soon

• T Codes and -99 Codes are used to cover emerging technologies on a

temporary basis.

• HCPCS (Healthcare Common Procedure Coding System) Codes are

intended to cover supplies, medical equipment and services billed by suppliers rather than by physicians.

Technologies that do not fall into the bundled payment system must obtain their own reimbursement code  Good Luck!!

It is Complex…SEEK ADVICE

Reimbursement = Coverage, Coding, Payment

Payment: The amount paid to the hospital or physician for using the therapeutic. Medicare is moving to link payment to the quality and efficiency of care provided.

• This will shift the focus of Medicare from paying providers and suppliers

based solely on the volume of services furnished to paying them based on the delivery of high quality, efficient health care.

Reimbursement Influencers

Summary

Key Activities are linked to your ecosystem. Need to define your:

• Minimal viable product
• Clinical trials
• Regulatory strategy
• Intellectual property
• Reimbursement

Questions?