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Disclaimer This Presentation contains forward-looking statements and information of Talaris Therapeutics, Inc. ("Talaris," "we," "our,") within the meaning of the Private Securities Litigation Reform Act of 1995. All sta

Key Takeaway: FREEDOM-1 CLINICAL UPDATE June 30, 2022 Disclaimer This Presentation contains forward-looking statements and information of Talaris Therapeutics, Inc. ("Talaris," "we," "our,") within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than

Full Press Release Details

FREEDOM-1 CLINICAL UPDATE June 30, 2022
Disclaimer This Presentation contains
forward-looking statements and information of Talaris Therapeutics, Inc. ("Talaris," "we," "our,") within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements
of historical facts contained in this Presentation, including statements regarding our strategy, future financial condition, future operations, projected costs, prospects, plans, objectives of management and expected market growth, are
forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "expect," "intend," "plan,"
"anticipate," "believe," "estimate," "target," "seek," "predict," "potential," "continue" or the negative of these terms or other comparable terminology.
Although we believe that the expectations reflected in these forward- looking statements are reasonable, these statements relate to our strategy, future operations, future financial position, future revenue, projected costs, prospects, plans,
objectives of management and expected market growth, and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different from any future
results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. Forward-looking statements in this presentation include, but are not limited to, statements about: the initiation, timing, progress,
results and cost of manufacturing and conducting clinical trials of FCR001, as well as our research and development programs and our current and future preclinical and clinical studies, including statements regarding the timing of initiation and
completion of studies or trials and related preparatory work, the period during which the results of the trials will become available, and our current and future programs; our ability to identify research priorities and apply a risk-mitigated
strategy to efficiently discover and develop additional product candidates; our ability to initiate, recruit and enroll patients in and conduct our clinical trials at the pace that we project; our ability to scale-up our manufacturing and processing
approaches to appropriately address our anticipated commercial needs, if FCR001 is approved; obtain and maintain regulatory approval of our product candidates, and any related restrictions, limitations or warnings in the label of any of our product
candidates, if approved; our ability to compete with companies currently marketing or engaged in the development of treatments that our product candidates are designed to target; our reliance on third parties to conduct our clinical trials and to
manufacture drug substance for use in our clinical trials; the size and growth potential of the markets for any of our current product candidates or other product candidates we may identify and pursue, and our ability to serve those markets; our
ability to identify and advance through clinical development any additional product candidates; the commercialization of our current product candidates and any other product candidates we may identify and pursue, if approved, including our ability
to successfully build a specialty sales force and commercial infrastructure to market our current product candidates and any other product candidates we may identify and pursue; the scope of protections we are able to establish and maintain for
intellectual property rights covering our product candidates and our Facilitated Allo-HSCT Therapy; our ability to retain and recruit key personnel; our expectations regarding government and third-party payor coverage and reimbursement; our
estimates of our expenses, ongoing losses, capital requirements and our needs for or ability to obtain additional financing; our expected uses of the net proceeds to us from this offering; the potential benefits of strategic collaboration
agreements, our ability to enter into strategic collaborations or arrangements, and our ability to attract collaborators with development, regulatory and commercialization expertise; our financial performance; developments and projections relating
to our competitors or our industry; the effect of the on-going COVID-19 pandemic, including mitigation efforts and economic effects, on any of the foregoing or other aspects of our business operations, including but not limited to our preclinical
studies and future clinical trials. We caution the Recipient not to place considerable reliance on the forward-looking statements contained in this presentation. The forward-looking statements in this presentation speak only as of the date of this
document, and we undertake no obligation to update or revise any of these statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Any forward-looking statements are based on management's current
expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press
release, including, without limitation, risks associated with the impact of the on-going COVID-19 pandemic where the Company has operations or does business, as well as on the timing and anticipated timing and results of its clinical trials; the
risk that the strategy and future operations of the Company, including the expected timing, enrollment, and results from FREEDOM-1 will not meet expectations; the risk that early data from the FREEDOM-1 study may not be predictive of or consistent
with future and/or final results; the risk that the results of Talaris' earlier clinical trials may not be predictive of results in any of the Company's ongoing or future clinical trials; and the risk that the Company may not be able to
successfully demonstrate the safety and efficacy of its drug candidates, including FCR001. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Company's Quarterly
Report on Form 10-Q for the quarter ended March 31, 2022, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Talaris' views only as of today and should not be
relied upon as representing our views as of any subsequent date. Talaris explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such
forward-looking statements. Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the
Company believes these third-party sources to be reliable as of the date of this Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from
third-party sources. In addition, all of the market data included in this Presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe
our own internal research is reliable, such research has not been verified by any independent source.
Talaris at a Glance Novel, single-dose,
investigational cell therapy with potential to transform standard of care in solid organ transplantation and multiple severe immune and non-malignant blood disorders Lead product, FCR001, in open-label Phase 3 to induce durable immune tolerance in
living donor kidney transplant (LDKT) recipients Compelling Phase 2 data Highly predictive, near-term surrogate marker of long-term success identified in Phase 2 Phase 3 protocol substantially mirrors optimized Phase 2; Orphan drug and RMAT
designation from FDA Reported encouraging initial results on first patients in late 2021 FCR001 has pipeline-in-a-product potential across multiple therapeutic applications Large market opportunity Two additional Phase 2 studies initiated Q4 2021
Robust, reproducible and fully in-house manufacturing Strong IP position and high barriers to entry Well-financed; ~$225M cash on hand as of March 31, 2022
Allogeneic Tolerance and Chimerism
Allogeneic tolerance: An approach to enable donor HSCs to coexist with recipient HSCs in the recipient's bone marrow ("chimerism"), and mature into mutually-tolerated, functional immune cells and blood cells Goal: facilitate
allogeneic tolerance by establishing durable chimerism Nobel Prize 1960* *Nobel Prize in Physiology or Medicine 1960 was awarded jointly to Sir Frank Macfarlane Burnet and Peter Brian Medawar for discovery of acquired immunological
Allogeneic Tolerance and Chimerism
Allogeneic tolerance: An approach to enable donor HSCs to coexist with recipient HSCs in the recipient's bone marrow ("chimerism"), and mature into mutually-tolerated, functional immune cells and blood cells Nobel Prize 1960* Goal:
facilitate allogeneic tolerance by establishing durable chimerism *Nobel Prize in Physiology or Medicine 1960 was awarded jointly to Sir Frank Macfarlane Burnet and Peter Brian Medawar for discovery of acquired immunological tolerance.'
Proprietary composition of donor's
CD34+ cells, Facilitating cells and T-cells FCR001: A Modified, Allogeneic HSC-based Therapy Unique, tolerogenic "non-stem cells" (CD8+, TCR-) Potential to: Promote stem cell engraftment in unmatched recipients Prevent GvHD
in mouse models Induce antigen-specific Treg Induce Breg Facilitating Cell FCR001 is administered with non-myeloablative conditioning, at doses and using protocols optimized over two decades of study Broad, issued composition of matter
Our Pipeline FREEDOM - 1 FREEDOM -
2* REPROGRAM: Solid Organ Transplantation FCR001 FCR001 or FCR002 Living Donor Kidney Transplant (LDKT) LDKT Delayed Tolerance Induction Deceased Donor Kidney Transplant FREEDOM - 3* RESTORE: Severe Autoimmune Disease FCR001 Scleroderma
REPLACE: Severe Blood, Immune, and Metabolic Disorders FCR001 Severe blood, immune, or metabolic disorders CANDIDATE INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 ~ 6,500/year ~ 6,000 to 10,000 ~ 16,500/year ~ 5,000 to 6,000/year TBD based on
indication US PATIENT POPULATION * Open IND permits us to move directly into Phase 2 based on existing FCR001 safety data ** Organ transplant population estimates based on UNOS/OPTN data; scleroderma estimates derived from epidemiology and
third-party market research; LDKT Delayed Tolerance Induction patient numbers based on 1 year to 18 months delayed from incident LDKT; Scleroderma estimated point prevalence of diffuse cutaneous SSc patients with early, rapidly progressing disease
and internal organ involvement
Unmet Need in Organ Transplant: Challenges
of Chronic Immunosuppression Immunosuppression is not disease-modifying; requires lifelong chronic immunosuppression Kidney toxicity ~35% of living donor transplants and ~50% of deceased donor transplants fail within 10 years1 Significantly
increased risk of cancer2 Hypertension, diabetes, high cholesterol, weight gain3 Cardiovascular (CV) issues are leading cause of post-transplant mortality Increased risk of serious infection4 High cost, pill burden (>20 pills/day for life) and
decreased QoL Cost ~$25K in first year and $5K-$10K annually for life of organ1 Poor compliance can lead to rejection or organ loss Sleep disturbance, CNS issues, depression, and other AEs affecting QoL "Ideally you want to avoid getting sick
or being around sick people because your immune system is suppressed. Unfortunately, in the world we live in, you're going to get sick. The first couple of times I got sick, I was terrified." - Male living donor kidney recipient in
40's "While others might breeze out the door in the morning, I am already preoccupied with preventing rejection, infection, and cancer." - FDA Voice of the Patient Panellist Sources: patientslikeme; The Voice of the Patient FDA
Meeting (Sep 2016): Patients who Have Received an Organ Transplant USRDS 2020 Annual Data Report, Fig 6.16: https://adr.usrds.org/2020/end-stage-renal-disease/6-transplantation Engels et al JAMA 2011; 306(17): 1891-1901 Nankivell BJ et al, Lancet
2011, 378:1428-37 Karuthu et al, Clin J Am Soc Nephrol. 2012 Dec;7(12):2058-70 QoL: Quality of life; CNS: Central Nervous System
Highlights from our Phase 2 Study (+
long-term followup)* 37 adult living donor kidney transplant (LDKT) patients were dosed with our therapy at two leading US transplant sites between 2009 - 2016 Across all HLA-mismatches 82% success rate (14 of last 17) once key parameters were
optimized * Data as of January 31, 2022. Includes 33 patients under Phase 2 protocol and 4 compassionate use patients ** One year after transplant *** Kienzl-Wagner 2018, Lim 2019, Moroni 2019 Median follow up: >6 yrs Six patients > 10 years
Longest >12 yrs Recurrence ordinarily seen in 20% - 60% of patients*** **
Strong Phase 2 Results Across All
Degrees of HLA-Match 19/26 (73%) durably off all chronic immunosuppression had HLA match of 3 or less between LDKT donor & recipient Comparable kidney and patient survival for all FCR001 vs standard of care (SoC) LDKT patients FCR001 safety
& tolerability data generally consistent with separate SoC kidney transplant + allogeneic HSCT with non-myeloablative conditioning No acute rejection or donor-specific antibodies in FCR001 patients off immunosuppression Number of HLA matches
between donor & recipient # of patients Data as of January 31, 2022 Phase 2 FCR001 patients weaned off all chronic immunosuppression
Phase 2 Three- and Six-Month Chimerism
Results Were Highly Predictive of Durable Immune Tolerance "Chimerism" % of recipient's T-cells that are donor-derived Simple blood test, measured at multiple time points 26/29 patients (90%) who achieved chimerism at month 3 were
able to be weaned off chronic immunosuppression (IS) 26/27 patients (96%) who achieved chimerism at month 6 were able to be weaned off chronic IS Every patient weaned off chronic IS by month 12 has remained off chronic IS for full duration of follow
up Median follow up >6 years Longest follow up >11 years Values are mean +/- standard deviation. N indicates the number of FCR001 treated patients weaned off IS at approximately one year post-transplant for whom % whole blood and T-cell donor
chimerism were measured at that time point 50% chimerism Data as of January 31, 2022
FREEDOM-1 Phase 3 Registration Study
STUDY OVERVIEW Study Design Open-label, randomized, controlled, parallel group study of FCR001 in 120 first time, adult living donor kidney transplant (LDKT) recipients, randomized 2:1 between FCR001 : standard of care (SoC) Five-year follow up for
safety Protocol; inclusion / exclusion criteria Near-identical to optimized Phase 2 protocol Primary Endpoint Proportion of FCR001 recipients who are free from chronic immunosuppression, without biopsy proven acute rejection (BPAR), at Month 24
post-transplant Key Secondary Endpoint In FCR001 recipients only, no meaningful decline in renal function from post-transplant baseline (Month 1) to Month 24 Additional Endpoints Chimerism, kidney function, safety Sites / Territory Targeting ~20
sites in U.S. (17 active sites as of June 15, 2022) Neither primary nor key secondary endpoint involves statistical comparison to the SoC patients
We Now Have 17 Active FREEDOM-1 Sites
Weill-Cornell Georgetown Mayo AZ Scripps Oregon U. Nebraska U. Michigan Northwestern Ohio St U. Minnesota Mayo Rochester Baylor UCSF U. Penn VCU Duke Mayo Jacksonville Data as of June 15, 2022
Phase 3 Update: Enrollment,
Demographics 22 1 13 10 different clinical sites have enrolled D/R pairs Screen Fail Dosed Pending Enrollment & Demographics Active 8 Control 5 7 1 Withdrew/Other 7 D/R pairs successfully dosed at 5 different sites Pending 2 4 2 Withdrew Dosed
Data as of June 15, 2022
Study Continues to Enroll Across
Degrees of HLA Mismatch HLA Mismatch of FREEDOM-1 Subjects (n=7) In addition to HLA mismatching data, high-resolution (HR) matching data (using a 12-point scale) is used in the BMT medical community. HR matching, however, is not available at all
sites. Pairs for which HR matching data is available include 3/12, 6/12, 6/12 and 7/12 matches. # of donor/recipient pairs
Phase 3 Update: FCR Chimerism and
Chronic IS Status * Chimeric: Achieved and maintained >50% T-cell chimerism at each designated study visit timepoint All FCR-001 patients have achieved and maintained chimerism* No instances of BPAR or DSA in any FCR-001 patients All have
maintained stable kidney function Longest follow up: 24 months with no BPAR Data through June 15, 2022 Time since kidney transplant # of Patients Dosed # of Patients Achieving Chimerism at each time pt <3 months >3 months >6 months >12
months Off Anti-Rejection Meds 3 100% (3/3) 100% (3/3) 2 100% (2/2) NA 1 100% (1/1) NA 1 NA 7 TOTAL Chimeric* through 6-mth visit NR Not reported; patient has not reached 3-month timepoint Chimeric* at 3-mth visit Chimeric* through 12-mth visit
Phase 3 Update: Safety Profile Summary
of safety profile in FCR001 patients AEs and SAEs observed are consistent with those generally expected with kidney and allogeneic stem cell transplantation involving non-myeloablative conditioning No events occurred that caused data monitoring
committee (DMC) to stop the study; no stopping rules triggered Three cases of low-grade aGvHD; all cases were treatment responsive and resolved Cases were grade II, with symptoms limited to skin and/or GI One of these three patients also diagnosed
with moderate cGvHD and is responding to treatment One of the patients with aGvHD who is more than 12 months post-transplant has been successfully weaned from tacrolimus and MMF Trial enrollment continues without interruption Talaris proactively
conducted a full review Review findings and subsequent recommendations reviewed and endorsed by both external scientific advisory panel and DMC * Data through June 15, 2022
Phase 3 Update: GvHD Review &
Protocol Adjustment Plerixafor introduced in mid-Phase 2 as option for donor mobilization Used in mobilization protocol to reduce potential need for second mobilizations Used much more frequently in Phase 3 than Phase 2 Identified a correlation
between aGvHD cases and increased use of plerixafor in Phase 3 Evident in four of five aGvHD cases when analyzing across Phase 2 and Phase 3 cohorts Plerixafor was associated with increased cell counts and decreased recoveries of FCs in our product
Last updated: Jun 30, 2022