How to Design Your Tech Transfer System to

Maintain Consistency During a Complete Site

Movement

OTCQB: MBVX

Marvin Peterson, Ph. D.

Sr. Director

Manufacturing

mpeterson@mabvax.com

Global Bioproduction Summit

December 13, 2016

2

DISCLAIMER

Forward Looking Statements

This presentation contains forward-looking statements and projections. The company makes noexpress or implied representation or warranty as to the completeness of this information or, in thecase of the projections, as to their attainability or the accuracy and completeness of the assumptionsfrom which they are derived, and it is expected that each prospective investor will pursue his, her, orits own independent investigation. It must be recognized that estimates of the company’sperformance are necessarily subject to a high degree of uncertainty and may vary materially fromactual results. In particular, this presentation contains statements, including without limitation theprojections, that constitute “forward-looking statements” within the meaning of the private securitieslitigation reform act of 1995. These statements appear in a number of places in this presentation andinclude, but are not limited to, statements regarding the company’s plans, intentions, beliefs,expectations and assumptions, as well as other statements that are not necessarily historical facts. Thecompany commonly uses words in this memorandum such as “anticipates,” “believes,” “plans,”“expects,” “future,” “intends,” and similar expressions to identify forward-looking statements andprojections. You are cautioned that these forward-looking statements and projections are notguarantees of future performance and involve risks and uncertainties. The company’s actual resultsmay differ materially from those in the forward-looking statements and projections due to variousfactors, including competition, market factors, general economic conditions and those described in the“risk factors” section. The information contained in this presentation describes several, but notnecessarily all, important factors that could cause these differences.

3

♦ HuMab Discovery Platform: antibody-based products derived from the human

immune response to cancer

– Developed platform for antibody discovery resulting in portfolio of fully human antibodies

– Early innovator in harnessing the natural human immune system in unique and proprietary ways to

create new products

– Integrated approach to development of cancer diagnostics along with therapeutics

♦ Scientific hypothesis

– Vaccination of patients elicits protective antibody response aimed at killing residual disease

– Natural human antibodies elicited from vaccinations are beneficial for novel targeted, off the shelf,

diagnostics/ therapeutics for patients with cancer

– Tumor-associated carbohydrate antigens present ideal targets for antibody-based therapy not yet

fully exploited

♦ Collaborations

– Memorial Sloan Kettering Cancer Center provides source of patient blood samples for our

discovery efforts, clinical trial site, and manufactures PET imaging clinical materials

– Heidelberg Pharma assists with development of conjugates for ADC program

– Rockefeller University collaborates with development of next generation human 5B1 antibody

– Juno Therapeutics has option to potentially use two binding domains for CAR development

candidates

MABVAX COMPANY BACKGROUND

4

MABVAX DISCOVERY PLATFORM: THERAPIES DERIVED FROM THE NATURAL HUMAN IMMUNE RESPONSE

Focused Discovery• Vaccination drives specific

immune response

• Survey response across multiple

patients

• Single B-cell interrogation yields

novel antibodies

• Native human antibodies

generated against validated

vaccine antigens

• Patient samples received from

trials in SCLC, sarcoma,

melanoma, neuroblastoma,

breast, colon, and ovarian

cancers

Screening• Highly efficient screening

against pre-identified targets

• Recovery of fully human

natively paired heavy and light

chains

• Identification of antibodies with

superior selectivity, affinity, and

key characteristics

• Library of fully human

antibodies against multiple

targets

Optimized Therapy• Fully human antibodies have

natural advantages; target

specificity while minimizing

cross reactivity and

immunogenicity

• Integrated development

platform includes

complementary immuno-PET,

diagnostic, ADCs and

radioimmunotherapy

5

MABVAX HAS RICH PIPELINE OF POTENTIAL MAB PRODUCTS

Program Target Discovery Pre-IND Phase 1 Phase 2 Commercial Rights

Monoclonal Antibody Programs

MVT-5873 Therapeutic Pancreatic & Colon Cancer1

NCT02672917 WW

MVT-2163 PET-Imaging

Pancreatic & Colon Cancer1

NCT02687230

WW

MVT-1075 Radioimmunotherapy

Pancreatic & Colon Cancer

WW

HuMab 5B1-ADC Pancreatic & Colon

Cancer

WW

HuMab 5B1 – Fc Optimization

Pancreatic & Colon Cancer

WW

HuMab-GD2 Sarcoma & Neuroblastoma

WW

HuMab-GD3 Melanoma, Sarcoma, Neuroblastoma

WW

HuMab-GM2 Multiple Epithelial Cancers

WW

HuMab-Tn Breast cancer WW CAR Programs

Various domains TBD WW

1FDA approved clinical study for pancreatic cancer and other CA19-9 positive malignancies

including colon, lung, breast, stomach and other cancers

6

Tech Transfer: The Plan

♦ Process Development and tech transfer targeted for GMP production in stainless steel reactors in US

– CMO near our Clinical Research Site

– 3 demonstration runs at 12L scale

– Fed-batch process CMO had previously demonstrated to be directly scalable to 200L GMP manufacturing

– Typical mAb Process

Upstream

Cell Bank Vial

Seed Train Expansion

Main Bioreactor

Clarification

Downstream

Clarified Harvest

Protein A, Viral Inactivation and Neutralization

AEX Chromatography

CEX Chromatography

Viral Filtration

UF/DF

7

Tech Transfer: The Plan Changes

♦ CMO acquired during tech transfer

– No longer will run our production in the US, but will transfer

to another of their acquisitions in Europe

– New quality systems

• 2 acquired sites with their own quality systems integrating

with a 3rd quality group

• New manufacturing equipment

–No stainless steel, all SUBs

–No prior tech transfer knowledge between sites

♦ Required tech transfer to 250L SUB for Toxicology production

♦ Team of consultants

8

Tech Transfer: Risk Assessment

♦ Risk Assessment performed across each individual unit

operation

– Minimal, Low, Medium, High rating

– Example: Downstream: 168 minimal, 85 low, 2 medium (255 total)

Step # of parameters

Minimal

Risk Low Risk

Medium

Risk High Risk

To be

verified* Risk Mitigation Actions

Key Accepted low risk differences

development - Tox

Key Accepted low risk differences

development - GMP****

Protein A 92 50 31 0 0 11

* Add mixing instructions in PP for VI titrations (low pH and neutralization) -

row 100 and 101

* Adding pre-use HETP/Ass testing - row 98 and 97

* Document UV meter path length in PP890 - row 84

* Calculate actual # of cycles required in clarified harvest PP - row 25, 87

* Specify in PP890 that step is run at room temperature - row 28

* Correct documentation (PD and TTP) - row 55, row 72, row 78, row 91

* Document and control clarified harvest hold time at RT and 2-8 deg C - rows

83, 85, 86, 87

* Transfer of low pH pool to a secondary

container

* Column packing storage solution

* Column packing qualification buffers

* Column bed height target increased to

maximum of range

* Transfer of low pH pool to a secondary

container

* Column packing storage solution

* Column packing qualification buffers

* Column bed height target increased to

maximum of range

AEX 56 39 9 2** 0 6

* Specify equilibration samples to be pulled right prior to load - row 66

* Document UV meter path length in PP - row 51

* Clarify hold time tracking in PP - rows 63, 64, 64

* Step is a key work horse in the process - evaluting real time performance

evaluation options ***

* Load adjustment dilution w/w vs. v/v

* Sanitization and equilibration residence

time

* Order of operations - 0.2 um filtration post

load adjustment

* Lower Sartobind Q loading - row 38

* Stop collect options***

CEX 91 60 18 0 0 13

* final PP updating/review - wash 2 volume (row 53), pH equil range (row 34)

* Document UV meter path length and start/stop collect in PP - rows 59,60

* Add expiry checks to PP - rows 85, 86

* Add PP instruction to pull equil samples right prior to load - row 88

* Specify dirty column hold time in PP - row 89

* Column packing procedure (solutions,

residence time) -rows 91,95, 98

* Target column bed height increased - row

91

* 2 POROS HS cycles, load adjustment

performed for both cycles at once - row 83

* Column storage solution - row 74

* Target column bed height increased -

row 91

Viral Filtration 46 19 27 0 0 0

* Evaluate harvest/in-process pool amounts of protein to determine if any

pre-emptive actions are required for filter loading (planning for high end)

* Initial filter handling (WFI flush,

sanitization) not performed - rows 12-23

* No filter integrity testing performed - row

45

* Filter sizing planning for going towards

upper end of load rates tested during

development - rows 31, 32, 34

9

Tech Transfer Risk Assessment Summary

♦ Outcome was a clear understanding of the path forward, despite

having completely different equipment and analytical methods

for the process we were transferring.

♦ Required much effort in troubleshooting and working our way

around these differences

♦ These tech transfer challenges led to multiple failed batches

♦ Required complete analytical analysis and comparability through

each step in all unit operations before moving forward

10

Tech Transfer: The Transfer Moves Forward

♦ Formulation Development showed freezing in PBS led to

aggregation

– In-process sample storage adjusted to 2-8 °C

♦ Control points established downstream

– Viral clearance, aggregation removal

♦ Ran 250L SUB simultaneously with a 5L side run to demonstrate

tech transfer

– Bioreactor scaled based on power per unit volume

♦ Once transfer was demonstrated, scaled for 500L GMP

production

♦ Logistics are critical

– Drug substance in particular

11

Cell Growth – Viability and Viable Cell Density

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Via

bil

ity (

%)

VC

D (

cell

s/m

L)

Time (days)VCD PNJ 12L BRX2 VCD PNJ 12l BRX3 VCD 5L TOX#2 VCD 250L TOX#2 VCD 500L G#1 VCD 500L G#2

Viability PNJ 12L BRX2 Viability PNJ 12L BRX3 Viability 5L TOX#2 Viability 250L TOX#2 Viability 500L G#1 Viability 500L G#2

12

Titer

0 2 4 6 8 10 12 14 16 18 20

Tit

er

(g/L

)

Time (days)

PNJ 12L BRX1

PNJ 12L BRX2

PNJ 12l BRX3

5L TOX#2

250L TOX#2

500L GMP#1

500L GMP#2

13

Product Quality

Batch Analysis MVT-5873 Drug Substance

12L 250L SUB 500L SUB (GMP)

Test Standard Deviation

Potency: Binding ELISA 9%

SEC (LMW) 0.02%

SEC (Main) 0.01%

SEC (HMW1) 0.00%

SEC (HMW2) 0.03%

CEX: Acidic 1.6%

CEX: Main 5.5%

CEX: Basic 4.6%

Residual DNA 0.98

Residual Protein A 0.23

Residual HCP 0.64

Also compared pH, Osmolality, Identity, SDS-PAGE, Endotoxin, and Bioburden

14

The Key Do’s and Don’ts

♦ Insist upon complete analytical analysis

– In-process product comparison across each unit operation and for end product

– Shows product consistency

♦ Risk assessment across each unit operation

♦ Insist upon reports (contractually)– Development

– Tech Transfer

– Campaign

♦ Constant oversite

♦ Frequent site visits during development and engineering

♦ Put a person in plant for GMP runs

♦ Consider strongly the difficulty to troubleshoot and provide oversite of a company on a different continent

♦ DON’T– Go to a CMO being purchased if possible!

Harnessing the Human Immune System To Diagnose and Treat Cancer

MabVax Therapeutics

David Hansen

Paul Maffuid, PhD

Wolfgang Scholz, PhD

Ritsuko Sawada, PhD

Dennis Gately, PhD

Sara Bancroft

Kevin Mudd

Aleksandra Marinkovic-Petrovic

Consultants

Scott Rudge, PhD RMC Pharma

Maria Wik, PhD RMC Pharma

Leticia Sanchez, PhD RMC Pharma

Deborah Quick, PhD RMC Pharma

Raymond Nims, PhD RMC Pharma

Acknowledgements

Research Supported byNIH/NCI CA128362

HHSN261201300060C

NIHR42CA128362