Bench to Bedside: Oncology Drug Product Development and Target Commercialization

1. Bench to Bedside: Oncology Drug Product Development and Target Commercialization April 2005 Eric Malek Vice President, Corporate Development Allos Therapeutics, Inc 11080 CirclePoint Road, Suite 200 Westminster, CO 80020 303-426-6262 malek@allos.com

2. Academic Collaborations- Biotech Perspective • Allos Company Background • Allosand IndustryApproach to Licensing / Acquiring Products • Allos Portfolio: History of Academic Collaborations • EFAPROXYN™ – Overview of discovery to market • Pralatrexate • RH1 • Corporate Perspectives on Drug Development • Formulation • In-vitro • In-vivo • Clinical

3. Allos Therapeutics is a biopharmaceutical company focused on developing and commercializing innovative drugs for improving cancer therapy

4. Allos Background • Founded in 1994 • 55 employees headquartered in Westminster, CO • March 2000 IPO; (NASDAQ: ALTH) • Three novel products targeting large medical markets in clinical development • Focus in oncology clinical development and commercialization in US

5. Allos Product Portfolio

6. Academic Collaborations- Biotech Perspective • Allos Company Background • Allos and Industry Approach to Licensing / Acquiring Products • Allos Portfolio: History of Academic Collaborations • EFAPROXYN™ – Overview of discovery to market • Pralatrexate • RH1 • Corporate Perspectives on Drug Development • Formulation • In-vitro • In-vivo • Clinical

7. Allos: In-Licensing as a Strategy • No in-house drug discovery programs – financial, facilities and human resource challenge • Permits operation in “semi-virtual” mode • Leverages expertise in drug development – IND to NDA • Valuation driven by clinical development milestones • Ad-hoc reviews and evaluations hold commercial strategic value • Foster relationships with experts • Remain opportunistic and aware of competitive environment • Positioned to execute quickly as corporate objectives evolve • Most top tier biotechs and pharmas proactively balance internal discovery with in-licensing • Many fall back on licensing in response to pipeline gaps and product setbacks

8. Allos In-Licensing Focus Leverage expertise in oncology clinical development • Focus on clinical and IND-stage opportunities • Preference for synergistic opportunities • Small molecules – manufacturing • Similar target indications – clinical development • Radiosensitizers – target physician audience • Cytotoxics – differentiation approach • Supportive Care – XRT and chemo side effects • Opportunistic: MAbs, novel targeted approaches, novel MOAs • No vaccines, cell therapies, uncharacterized plant / animal extracts

9. Allos In-Licensing Process

10. Large Pharma In-Licensing Process

11. Recommendations to Academia for Approaching Industry • Many functions and levels of mgmt. involved in decision making • Many pathways to a no decision • Many opportunities competing for attention, time and resources to evaluate ------------------------------------------------------------------------------------------- • Understand the decision process in companies you target • Build relationships with the scientists / clinicians • Present data on differentiation and product/research or commercial synergies - less info and targeted • Understand the data points that “sell” to reviewers • Understand the downstream regulatory impacts of research decisions • Address IP opportunities early on

12. Academic Collaborations- Biotech Perspective • Allos Company Background • Allosand IndustryApproach to Licensing / Acquiring Products • Allos Portfolio: History of Academic Collaborations • EFAPROXYN™ – Overview of discovery to market • Pralatrexate • RH1 • Corporate Perspectives on Drug Development • Formulation • In-vitro • In-vivo • Clinical

13. In-Licensing History- EFAPROXYN • Company founded in 1994 on technology licensed from Virginia Commonwealth University (VCU) • VCU research in allosteric modifiers of hemoglobin underlies Allos’ lead clinical compound, EFAPROXYN • Result of collaboration between Donald Abraham at VCU and Nobel Laureate Max Perutz Efaproxiral (RSR13) • Attractive platform for emerging biotech  broad clinical applicability • Hypoxia relevant to indications in oncology, cardiovascular, surgery and critical care specialties • Favorable terms for pre-IND compound • Fundable opportunity

14. EFAPROXYN Development Timeline ENRICH confirmatory study initiated Phase 2 in brain metastases Fast Track granted for brain metastases Expand Development 1. primary (extra-cranial) indications 2. emerging regimens (Erbitux, Temodar, SRS) Original license agreement Phase 2 in CABG Phase 3 in brain metastases initiated Phase 1 in NSCLC (concurrent) initiated Phase 1b in solid tumors Phase 1/2 in cervical cancer initiated Phase 2 in GBM Market launch 1996 2000 2004 NDA filed MAA filed 2007 1994 PK study 1998 Phase 2 in NSCLC 2002 2006 Phase 1b in GBM Phase 1/2 in recurrent GBM initiated ENRICH enrollment complete INDs filed ODAC Phase 1b in surgery Approvable letter and orphan drug designation ALLOS IPO Phase 1b in angina TOTAL $207M $2M ‘94 $3M ‘95 $8M ‘96 $18M ‘98 $10M ‘99 $90M ‘00 $15M ‘02 $11M ‘03 $50M ‘05

15. In-Licensing History- Pralatrexate (PDX) • A novel antifolate (DHFR inhibitor) licensed from MSKCC, SRI, SoRI in January 2003 Background and Rationale for License • Differentiated among 100+ compounds evaluated in 2002 • Phase 2 single agent proof of activity in 2nd line NSCLC • Broad development program underway at MSKCC • Leverages internal expertise Unexpected Challenges • Manufacturing process improvements • Repeat Phase 1 dose escalation • Validate benefit of vitamin supplementation • Significant advances to NSCLC standard of care has complicated pathway to approval in lead indication

16. In-Licensing History - RH1 • Targeted cytotoxic prodrug licensed from CRUK, University of Colorado and Salford University in 2005 Background and Rationale for License • Interest in program dating from early 2002 • Resumption of Allos in-licensing activities (post ODAC) and CU commitment made 2005 execution possible • Near-term milestone - Phase 1 data available in 2005 • NCI sponsored pharm / tox and CMC work complete Potential Challenges • Reformulation might be necessary to avoid IP issues • FDA identifies IND gaps • Both situations involve development delay + additional expense

17. Academic Collaborations- Biotech Perspective • Allos Company Background • Allosand IndustryApproach to Licensing / Acquiring Products • Allos Portfolio: History of Academic Collaborations • EFAPROXYN™ – Overview of discovery to market • Pralatrexate • RH1 • Corporate Perspectives on Drug Development • Formulation • In-vitro • In-vivo • Clinical

18. Preclinical Drug Development PitfallsA Corporate Perspective- Formulation • Purity of agent being tested should be reasonable • At least 95% pure • Need a reproducible source of agent which can be scaled up in sufficient quantity for clinical trials • Solubility is a key issue and needs to be addressed early • Many agents are soluble in DMSO, but nothing else • Evaluate protein binding early • Consider oral formulation if: • Frequent dosing will be needed • Poor solubility in clinically relevant solvents

19. Preclinical Drug Development PitfallsA Corporate Perspective- In vitro studies • Advantages • Useful for early screening of analogs • Helpful in screening for synergy or sequence dependency • Inexpensive and quick • Disadvantages • Extremely poor correlation with clinical activity • Suggestion • Use only as a screening tool • Use cell lines that are well characterized and accepted • Avoid performing studies in solvents with no clinical counterpart (i.e., DMSO) • Should not be only data related to antitumor activity

20. Preclinical Drug Development PitfallsA Corporate Perspective- In vivo studies • Advantages • Useful for early screening of analogs • Helpful in screening for synergy or sequence dependency • Better correlation than in vitro studies with clinical activity • Disadvantages • Costly and time consuming • Suggestion • A necessity for proving activity!! • Use cell lines that are well characterized and accepted (PC3, HT29, MiaPaCa, MDA-231) • Design studies based on industry standards • Well characterized growth curves with small growth variation • Appropriate sample sizes (10 animals / group) that allows for statistical analysis • Avoid intratumor injection to deliver drug • Use relevant controls and include pharmacokinetics

21. Clinical Drug Development PitfallsA Corporate Perspective - Clinical Studies • Consider multiple Phase 1 studies using different schedules • Quality of data is key • Most Phase 1 and 2 studies conducted solely by academic centers result in data that cannot be used by companies for NDA purposes • Data should stand up to outside auditing • Strongly consider the use of an IRRP to review and confirm all “responses” • Avoid the “single center syndrome”