Immunotherapy Against Metastasis

1. Immunotherapy Against Metastasis Non-confidential Presentation December 2018

2. Immuno-oncology, T-cell Activation RhoVac is developing a novel immuno-oncology product for treatment of cancer metastasis • Utilize body’s own immune system, through T-cell activation, to fight cancer cells • RhoVac’s drug candidate, RV001, targets the protein RhoC which is documented to be overexpressed in almost all cancer cells having metastatic potential ⃰ We cooperate with the body's immune system - instead of working against it ⃰Clark et al. 2000; Hakem et al. 2005; Wenandy et al. 2008; Karlsson et al. 2009; Yang et al. 2016; et al December 2018

3. Targeting Cancer Progression in Early Stage RV001 - Prevent or Reduce Relapse in Prostate Cancer Patients December 2018

4. EMA Scientific Advice: Conclusions • Critical CMC questions resolved – no further action is required • Phase IIb trial, as proposed, can commence based on the existing pre-clinical data – no additional studies required • Safety monitoring for the proposed Phase IIb trial is agreed • A biologically active dose has been demonstrated by the current Phase I/II trial – the proposed dose for the Phase IIb trial is agreed • Phase IIb trial patient population is agreed: “there is a clear window to treat with RV001 between radical prostatectomy and Biochemical Recurrence” • The proposed clinical end-point – biochemical recurrence – is a relevant end-point • Additional end-points are under discussion and further scientific advice may be taken December 2018

5. FDA Public Workshop, 11th July 2018 FDA Oncology Center of Excellence Public Workshop: Development of Treatments for Localized Prostate Cancer The workshop was designed to discuss trial designs and suitable clinical trial endpoints for treatment of this patient population in the hope of advancing effective treatment options in this area. Workshop Comments: • High risk and medium risk patients should be offered treatment instead of active surveillance. • There is an unmet need for treatment of these patients • Treatment must be safe and well toleratedin context of active surveillance • Delay/Avoidance of morbidity from other treatments having short and long-term toxicity is a relevant endpoint, but cannot stand alone due to potential risk for bias FDA aligned with RhoVac position on treatment of proposed patient group. RhoVac will send meeting request to the FDA early 2019 for a pre-IND meeting. December 2018

6. Phase IIb Clinical Study - Planned A Phase IIb study of RV001, in Adult Males with Biochemically Relapsed Prostate Cancer Following Definitive Local Therapy • Patients biochemically relapsed following definitive local therapy (prostatectomy or radiotherapy) will be enrolled • Primary objective: To evaluate if RV001 can reduce PSA progression compared to control group. • Primary endpoint:Time to PSA progression, defined as the time from randomization to the date of first PSA ≥ twice the baseline value • Secondary endpoints: • Safety and tolerability • Delay the time to subsequent antineoplastic therapy initiation • Evaluate relationship between immunological response and biochemical response December 2018

7. Phase I/II Clinical Trial ⃰ - Completed Subject Group • Patients prostatectomised due to prostate cancer Objectives • The primary objective is to evaluate the safety and tolerability of RV001 Vaccine • The secondary objective is to investigate the RV001-specific immunological response before, during and after treatment • The exploratory objectives are to study the potential associations between PSA levels and immunological response and to preliminarily evaluate the progression-free survival (PFS) and overall survival (OS). Patient recruitment and treatment: • Patients are treated with 11 sc injections over approximately 30 weeks. • Recruitment of 22 patients completed July 2017 ⃰ ClinicalTrials.gov identifier: NCT03199872 December 2018

8. Phase I/II Clinical Trial : Study Results Primary Objective, Safety and Tolerability Safety • The primary endpoint of the study was the proportion of patients developing treatment related Grade 3, 4 or 5 toxicity in accordance with CTCAE, with the exception of fever. There were no treatment related Grade 3, 4 or 5 toxicity during the study Tolerability: • Good compliance to treatment • 21 of 22 patients completed all 11 vaccinations • No withdrawals due to safety • Patients only experienced mild (≤ Grade 2), reversible injection site reactions RV001 has been shown to be safe and well tolerated in patients with prostate cancer December 2018

9. Phase I/II Clinical Trial : Study Results Secondary Objective, Immunological Response • 18 out of 21 patients (86%) were considered as Confirmed Immune Responders as they demonstrated significant responses in two of the three samples taken during or after treatment RV001-mediated immune response is established and the selected dose is biologically active IFNγ ELIspot, Patient No: 018 December 2018

10. Phase I/II Clinical Trial : Study Results Exploratory objectives, Changes in Prostatic Specific Antigen (PSA), association to Immunological Response, Progression Free Survival (PFS) and Overall Survival (OS) Changes from baseline in Prostatic Specific Antigen (PSA) • No patients experienced a biochemical relapse over the treatment period of approximately 8 months Potential association between PSA and immunological response • As only two patients had measurable PSA, no meaningful association between PSA and immunological response could be explored. Progression Free Survival (PFS) and Overall Survival (OS) • As there were no patients who had a cancer status defined as progression and no patient that died during the study, no meaningful assessment of PFS or OS could be explored. December 2018

11. Development Plan – 2018 to 2021 (Q3) • Listing on AktieTorget (Spotlight) • Toxicological Study completed • Approval of CTA • Start of Clinical phase I/II Study • Completion of Clinical Study phase I/II • Immunological Analysis • Start of phase IIb trial • Late Stage CMC Development • Completion of Phase Ilb • Scientific Advice, EMA • Pre-IND Meeting, FDA • CTA Submission • PIP (Paediatric Investigation Plans) Ongoing Research Collaboration • Immunotherapy/immune-monitoring - University of Tübingen and Centre for Cancer Immune Therapy • Cancer stem cells – Lund University December 2018

12. Financial Information Top-line result of phase I/II Spotlight Stock Market 50 SEK Positive meeting with EMA 40 Completion of phase I/II treatment 30 20 Positive immune monitoring result 10 Sep Nov Jan Mar May Jul Aug 2018 December 2018

13. Back-up Slides December 2018

14. Use of Proceeds • Clinical Phase IIb Study in Prostate Cancer • Exploratory Clinical Study in Different Indication • Late Stage CMC Development • Continue Business Development • Continue Regulatory Development • Continue Research in Focused Areas December 2018

15. RhoC – A Prioritised Cancer Antigen • The National Cancer Institute ranks RhoC as a prioritized cancer antigen, ideal for cancer vaccine development4 • RhoC is silenced in normal cells • In normal cells RhoC is silenced: no interaction with the immune system and currently there has been no in-vivo studies demonstrating any function • In cells with metastatic potential, RhoC is overexpressed; the immune system identify these cells as “foreign” and eliminates them • RhoC is directly involved in tumor cell survival and progression • The direct role of RhoC in the process of metastasis formation has been shown. Down regulation or loss of RhoC expression reduces the motility of cancer cells and survival of metastatic cells, leading to drastic inhibition of metastasis1 • RhoC is expressed in almost all metastatic cancer cells • Over-expression of RhoC in metastatic cancer cells has been shown in majority of cancer types, and also several types of cancer stem cells , e.g. breast and head & neck2 • Mutations of RhoC in cancer are very rare3 • Thus antigen mutation and immune escape to therapy is not a limiting factor for effectiveness 1Hakem et al. 2005 2Rosenthal et al. 2012 and Islam et al. 2014 3COSMIC Database, October 2017 4Cheever et al. 2009 December 2018

16. Pre-clinical Evaluation in Human Cancer Cell Lines The drug candidate RV001 induces a specific and strong immune response against cells with over-expressed RhoC, and empowers the immune system to find and eliminate them • RV001 binds to the HLA molecule, forming a “fingerprint” or “flag” of RhoC on the cell surface • Spontaneous T-cell response towards RhoC. T-cells recognizing RhoC could be identified in blood samples from cancer patients • RhoC-specific T-cells kill tumor cells demonstrated by using human cancer cell lines as natural targets for killing by the T-cell Breast Cancer Melanoma Colon Cancer Killing of cancer cells of different origin by a RhoC specific T cell clone. Experiments were carried out at different T cell / tumor cell ratios (x axis) December 2018

17. RhoC Expression in Cancer Stem Cells RhoVac has started a research collaboration with Lund University to conduct more research on RhoC expression in prostate cancer stem cells (PCSC) • The collaboration is focused on: • Confirm overexpression of RhoC in PCSC • Can overexpressed RhoC in PCSC be a target for immunological treatment of PCSC? December 2018

18. IP Development AU – granted (Dec 2028) USA – granted (Mar 2032) • Continuation filed Japan – granted (Dec 2028) • Divisional Filing approved EU – granted (Dec 2028) Canada – pending • Extensions possible in all markets December 2018

19. UNIC IMMUNTERAPY AGAINST METASTASING CANCER Comtact: Anders Ljungqvist, CEO alj@rhovac.com Henrik Stage, CFO hst@rhovac.com December 2018