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Two organizations collaborating with WHV were given the opportunity for a poster presentation at the recent 2022 ISV Annual Congress, held in Quebec City, Canada on September 18-20 to present findings related to WHV’s product PDPHV.

One of the posters, presented by Dr. Stephen Walsh, Principal Investigator of WHV138 and a physician in the Division of Infectious Diseases at Brigham and Women’s Hospital in Boston, MA, highlights the recruitment success of WHV138. This single-site phase 1b trial has been fully enrolled with 42 volunteers after a nearly 11-month enrollment period despite the challenges imposed by the Covid19 pandemic, including the interference of Covid19 vaccination and booster needs for study volunteers who also adhere to a strict vaccination regimen of the investigational HIV vaccine product PDPHV. Electronic means of communication and data storage play a key role in the trial’s successful operations. Reaching the enrollment goal within a common recruitment time frame in the midst of the Covid19 pandemic is thanks to the use of social media platforms. By using the latest video conference tools, the team is able to hold periodic safety review meetings virtually. Moreover, regular monitoring visits are conducted through the remote review of the trial’s EDC system. These modern-day methods offer operational advantages for conducting trials in the future, even after the pandemic wanes.

The second poster showcases a study conducted at Dr. Lu’s lab at the University of Massachusetts Chan Medical School (UMMS) isolating an A32-like ADCC mediating monoclonal antibody (mAb) induced by the first generation PDPHV that was under investigation in the previous phase 1 trial DP6-001. This new mAb showed cross-clade gp120 binding and potent ADCC activities, reaching a level of magnitude like the gold standard mAb32, which was isolated from a chronically infected HIV-1 patient and serving as the ADCC benchmark in the HIV field. These findings indicate that PDPHV is capable to induce an immune response similar to that induced by HIV infection – clues that can help researchers advance towards new breakthroughs in the HIV vaccine field.

WHV’s HIV vaccine candidate PDPHV is currently the only product tested in humans that targets all four major circulating subtypes of HIV-1 responsible for the global HIV pandemic. WHV is pleased that two posters about PDPHV were presented at this year’s ISV Annual Congress.

The WHV138 Safety Review Board (SMB) successfully met on July 26, 2022, together with sponsor as well as protocol leadership representatives for the trial’s first periodic safety review. The board chair, Dr. Marnie Elizaga, together with board members, Dr. Michael Keefer and Dr. Yunda Huang, reviewed cumulative safety data – unblinded as to treatment arm –  from trial initiation up until everyone from Group 2 received at least their first vaccination. Since there were no major safety concerns identified, the trial will continue as planned. Thanks to the highly experienced clinical team who is running WHV138 very competently, the milestone for the next periodic safety review is approaching quickly. Thus, the second of a total of three SMB meetings will likely be held in mid-September. Overall, the trial is progressing well and on track to administer the last volunteer’s final vaccination by the end of this year, with the final safety follow-up visit anticipated to be in late fall of 2023.

At the recent AIDS2022 conference in Montreal, Canada, the International AIDS Society (IAS) formally launched the Global HIV Vaccine Enterprise Industry Partnership Group during the satellite session “Swinging into full gear: Strengthening industry engagement in HIV vaccine research and development”. This partnership – of which WHV is now a proud member – is a multi-stakeholder group aiming to support industry’s contribution to HIV vaccine R&D by addressing and minimizing barriers to engagement.

Dr. Shan Lu, the original developer of WHV’s polyvalent DNA/Protein HIV Vaccine PDPHV, attended the partnership program inaugural session at AIDS2022 on July 29^th, representing WHV as an industry partner. “We cannot successfully develop an HIV vaccine unless industry and academia work closely together”, Dr. Lu’s words during the panel discussion that perfectly summarize the history behind WHV. In 2018, WHV was brought to life as a small biotech startup that licensed PDPHV from Dr. Lu’s lab at the University of Massachusetts Chan Medical School (UMMS) to advance the HIV vaccine candidate through early clinical trial testing. As part of WHV’s product development program, the new biotech company quickly became the IND holder and sponsor of the currently ongoing phase 1b WHV138 trial testing the safety and immunogenicity of PDPHV. The preceding phase 1a HVTN124 trial, which was sponsored by the HIV Vaccine Trials Network (HVTN) and funded by the National Institute of Health (NIH), successfully concluded early last year. The HVTN124 trial tested PDPHV under a different vaccine administration regimen than WHV138 and showed that PDPHV has a good safety profile with remarkable immunogenicity data. The accomplishments of WHV’s clinical partners and considering that the phase 2 grade investigational vaccine product is already manufactured and ready for subsequent clinical testing demonstrate an unprecedented success story for a small biotech company like WHV in the HIV vaccine field. “Currently, there is no other industry entity in the world like WHV whose sole dedication is to develop a safe and effective HIV vaccine”, Dr. Lu points out, highlighting the need for closer collaboration between various stakeholders focusing on vaccine discovery, development, clinical research, manufacturing, and distribution in order to efficiently move HIV vaccine candidates from the bench to the clinic and to eventually use as a much-needed tool in the fight against the global HIV pandemic.

Despite the challenges the COVID-19 pandemic poses on many clinical trials, the phase 1b WHV138 trial is making great progress.  By July 9, 2022, one third of Group 1 (N=7) has completed their vaccination regimen. Thanks to the highly experienced study team at the Brigham and Women’s Hospital, the WHV138 trial continues to progress well.

After this fourth and final vaccination for Group 1, which is 12 months post the first vaccination, the study participants will be followed for a 12-month safety observation period before they have officially completed the study. The remaining two thirds of volunteers in Group 1 are expected to complete their full course of vaccination by the end of August. 

Group 2 is also making good progress.  Participants in this group receive five vaccinations over the course of 8 months, also followed by the 12-month safety observation period. In this group, all volunteers have already received their first and second vaccination. The very final vaccination is anticipated to be administered in December 2022.

WHV is proud to be partnering with such an experienced clinical team and would like to acknowledge the remarkable contribution of volunteers in the middle of new COVID-19 waves in the country.

Thanks to our highly experienced clinical team, the enrollment objective of a total of 42 study participants has been completed. With the recent enrollment of the 21st healthy volunteer into Group 2, the single-site WHV138 trial is now fully enrolled after 10 months of assiduous recruitment efforts. This marks a major milestone for the young biotech company WHV, who is a first-time IND holder and the sponsor of this phase 1b randomized, placebo-controlled trial.

As the vaccination regimen for Group 2 includes five vaccinations over the course of 8 months, the trial’s very last vaccination will be administered by late-December of this year, followed by a 12-month safety observation period. Thus, we can anticipate the entire trial to be completed before the end of 2023. So far, there have been no major safety concerns identified. Data analyses regarding the immunogenicity of the vaccine candidate PDPHV as used in WHV138 will follow and are expected to give additional insights into the very promising immunogenicity profile generated by the HVTN124 study – a previously conducted phase 1a trial testing PDPHV under a slightly different vaccination regimen.

PDPHV is currently the only vaccine formulation tested in humans that includes viral ENV antigens from all four major circulating HIV clades with the potential to elicit very promising immune responses without any major safety concerns. WHV is therefore eager to move their HIV vaccine candidate further through the next testing stages to explore vaccine efficacy. The team has already started to prepare for a larger scale study and is hoping to officially announce trial partners in the near future.

Today, on HIV Vaccine Awareness Day 2022, WHV would like to thank their partners for their crucial role in the vaccine development program of WHV’s second generation HIV vaccine candidate PDPHV. A team comprised of renowned HIV vaccine research groups, competent CROs, and talented individual specialists has been providing WHV with high quality products and expertise, assuring a smooth operation for the new biotech company over the past four years. WHV is grateful for their continued partnership and support, which has been essential in successfully moving PDPHV through the subsequent clinical testing phases.

More importantly, WHV wants to extent their gratitude towards the many volunteers who participated and continue to participate in the HIV vaccine trials, including HVTN124 and WHV138. Without all of the healthy individuals who volunteer as a research subject, the search for a safe and effective preventative HIV vaccine would not be possible. As the phase 1b WHV138 trial is almost fully enrolled, the investigation of the safety and immunogenicity of this polyvalent DNA/Protein HIV vaccine candidate is progressing well. Once the trial is completed and data can be analyzed, newly acquired knowledge from this study will help the entire HIV vaccine field advance towards finding a safe and effective HIV vaccine.

Today, WHV joins the world in commemorating World AIDS Day in remembrance of those who have lost their lives due to AIDS-related illness and to show support for those living with HIV. This world AIDS day, we reflect back on the achievements of the HIV vaccine research community in 2021 and acknowledge the ongoing critical need to accelerate the development of a safe and effective HIV vaccine in order to reduce HIV infections around the world.

Over the past year, WHV has accomplished two major clinical development milestones relevant for the fight against HIV: In March of 2021, the phase 1a HVTN124 trial evaluating the safety and immunogenicity of WHV’s polyvalent DNA/Protein HIV Vaccine (PDPHV) candidate formally concluded without the occurrence of any safety concerns and secondary analyses showed remarkable immunogenicity data. This trial was sponsored by the the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN). Results from HVTN124 were presented at the HVTN Full Group Meeting in May. Only a few months later in July, the subsequent phase 1b WHV138 trial was launched, aiming to further characterize the safety and immunogenicity profile of PDPHV in a simplified vaccination schedule. This is the first time for WHV to act as the sponsor of a clinical trial since the biotech company was established only three years ago. WHV138 is already half-way enrolled and is anticipated to conclude in the Fall of 2023. Plans for a phase 2 trial are already underway as WHV prepares to move the vaccine candidate into the next testing stage.

There is growing evidence that a safe and effective as well as globally relevant HIV vaccine needs to not only be multigenic, polyvalent, and heterologous, but also be able to elicit a multi-factorial immune response in order curb the HIV pandemic manifesting a large HIV-1 subtype diversity. The vaccine candidate PDPHV is currently the only product tested in humans that targets all four major circulating subtypes of HIV-1 responsible for the global HIV burden. Its formulation is based on decades of research conducted by Dr. Lu’s lab at the University of Massachusetts Medical School (UMMS) in Worcester, MA. The vaccine consists of a 5-plasmid Env (A, B, C, E)/Gag (C)-expressing DNA vaccine and a recombinant gp120 protein vaccine of which the antigens are matched to the DNA plasmids. Results from Dr. Lu’s pre-clinical studies in rabbits, as well as early phase trials in humans indicate that when used in a DNA/Protein prime-boost regimen, PDPHV has the potential to elicit cross-protective, high magnitude and large breadth immune responses. With such a low-risk safety profile and very promising immunogenicity results, the vaccine candidate PDPHV could have a major impact on the HIV vaccine field, advancing it further towards developing a safe and effective HIV vaccine that can be applied worldwide.

WHV is honored to engage with a number of stakeholders joining efforts in ending the HIV pandemic that has caused hundreds of thousands of deaths and is still affecting millions of people today. Together with leading HIV vaccine researchers and renowned infectious disease specialists, WHV strives to advance the HIV vaccine field and aspires that AIDS will one day be a vaccine preventable disease.

In less than 4 months since the start of the WHV138 trial, the clinical team enrolled 21 healthy volunteers into the study and thus completed the enrollment objective of the first of two groups. Now that Group 1 is fully enrolled, the clinical team will continue their screening efforts and start enrollment of Group 2 soon, anticipating to fully enroll the whole study by early 2022.

WHV138 is a phase 1b single site randomized placebo-controlled trial evaluating the safety and immunogenicity of the polyvalent DNA/Protein HIV vaccine product PDPHV, which is tested in two groups receiving two different vaccine regimens. Group 1 receives the DNA and Protein+adjuvant vaccines injected separately in each upper arm; 4 doses are given over the course of 12 months. Group 2 will receive the DNA and Protein products mixed together without the inclusion of an adjuvant; 5 doses are given over the course of 8 months. Both groups will be followed up for an additional 12 months to monitor the safety profile of the PDPHV product.

The PDPHV vaccine candidate consists of two components, a 5-plasmid DNA vaccine covering the HIV clades A, B, C, and AE, and a 4-valent recombinant gp120 protein vaccine, matched to the DNA plasmids. PDPHV is the first and only vaccine formulation tested in clinical trials that includes viral ENV antigens from all four major circulating HIV clades, presenting a vaccine candidate that could have a significant impact on the global HIV burden.  This product was previously tested in the HVTN124 phase 1a trial and has shown excellent safety and immunogenicity results. It is now tested with a revised vaccination regimen and will further be tested in a phase 2 trial to finalize the design of vaccine dosing and scheduling.