Platform

Science

Our Engine: The PepGenesis™ Platform

A Closed-Loop GenAI Engine​

Our platform integrates AI-guided design with high-throughput wet-lab data in a rapid Design-Make-Test-Analyze (DMTA) cycle.

PepFusion™ (Make): Constructs massive, tunable
peptide libraries (up to 1015 variants) to mimic protein

PepSelect™ & PepPenetrate™ (Test): High-throughput screening for optimized structure, stability, and cell and tissue permeability.​

PepGenesis™ (Analyze): Our GenAI algorithm analyzes experimental data to rationally design the next, superior evolution of peptides.

Engine that combines rational sequence design, tunable library construction, high-throughput selection, and experimental feedback to drive the directed evolution of peptide therapeutics with precision and speed.​

PepFusion: Engineer Peptides to Mimic Protein Interfaces​

Size: up to 1015 variants for interface mimicry

CHALLENGE

Naturally occurring protein-protein interactions often have disparate epitope binding that is held in place by complex protein scaffold.​

DESIGN

PepFusion™ Directs evolution by rearranging sequences involved in protein-protein interactions to create custom libraries. ​

Size: up to 1015 variants for interface mimicry

PepSelect™ & PepPenetrate™: High-Throughput Selection to Expedite Lead Optimization​

1015 variants can be screened in <5 weeks​

Leads are inserted into the structural features of preselected scaffolds to optimize peptide structure in a high-throughput screen. Experimental data is used for rational sequence design with PepGenesis™.

1015 variants can be screened in <5 weeks​

Sequencing data from cell nuclei is analyzed by PepGenesis™ to optimize localization.

Subcutaneous injection of advanced Supernatural Peptide™ concepts enables identification of blood brain barrier-penetrant leads, which are refined by PepGenesis™​.

PepGenesis™: To Expedite Lead Optimization​

PepGenesis™ is a GenAI-guided directed evolution platform that leverages high-fidelity selection data from proprietary molecular evolution experiments. By integrating these data with advanced predictive modeling, PepGenesis™ identifies optimal peptide amino acid compositions to maximize selectivity, affinity, permeability, stability, and water solubility for ease of formulation.​

Assesses the directional evolution of peptide structure, length, mass, isoelectric point, net charge, hydrophobicity, and “hot spots” for protease cleavage.

Inserts amino acid substitutions, additions, and subtractions for improved selectivity, affinity, stability, and when necessary, cell and tissue permeability.​

Superior AI

Differentiated from other GenAI Platforms​

Alcamena’s Unique Position in the Peptide Therapeutics Space

The Only Directed Evolution Platform with Clinical Validation and Verified Blood–Brain Barrier Penetration

↔️ Swipe to view full table
Company
Modality​
CNS Access
Directed Evolution​
Time to IND
Clinical Assets

Alcamena

Supernatural Peptides™

10–18 months

Insilico

Small ​Molecules

3 years​

Recursion

Small ​Molecules

2 Years

Generate

Antibody

4 Years​

Parabilis

Helicon™ peptides

2-3 Years​

Google search terms: Insilico, ISM001, Recursion, REC-4881, Generate, GB-0895, Parabilis, FOG-001

Speed Advantage

10-18 months vs 2-4 years for competitors

Unique Capability

Peptide platform with proven CNS penetration

Clinical Validation

ASCT-83 in Phase 1 proves platform

Critical Differentiator: Most therapeutic peptides fail to cross the blood-brain barrier due to size, polarity, and efflux transport. Alcamena’s PepPenetrate™ screening solves this problem, enabling access to intracellular CNS targets.

Platform Validation

Validation: ASCT-83 (Clinical Phase 1)​

Months to IND Acceptance​

A First-in-Class CNS Asset​

ASCT-83 is a potent (KD = 3.5 nM), CNS-penetrant peptide targeting the “undruggable” intracellular REST:CTDSP1 interaction.

This asset proves our platform can rapidly create clinical stage drugs for the most challenging targets.​

Achievements

Proven Traction and Accelerated Achievements​

Platform Validation & Speed to Clinic

Our GenAI-guided PepGenesis™ Platform delivers unprecedented speed and capability, significantly de-risking the pipeline.​

↔️ Swipe to view full table
Metric
Alcamena Performance​
Industry Standard​
Impact

Speed to IND-Ready​

10-18 Months​

2 – 4+ Years

Accelerates path to clinical data and market entry

Platform Validation

ASCT-83 in Phase 1 Clinical

Pre-clinical / Discovery

De-risks technology with human data

Target Access

CNS / Intracellular (REST:CTDSP1)

Extracellular Targets Only

Unlocks the previously “undruggable” proteome

Financial & Development Milestones​

Demonstrated ability to develop drugs, secure funding, and generate partnerships​

Proven Execution​

$17M in Contracts Secured Since 2018: Establishing strong early financial and partnership traction.

Validated Access to CNS Targets: ASCT-83 demonstrates the ability to safely and effectively deliver Supernatural Peptides™ across the blood-brain barrier.

Robust Pipeline: Multiple assets in clinical, Pre-IND, or preclinical stages, targeting massive markets, including metabolic disorders, chronic pain, and autoimmune diseases.

Case Studies in Development​

ASCT-83: First-in-class CTDSP1:REST inhibitor with compelling data across multiple complex indications (obesity, neuropathic pain, neurodegeneration, glioblastoma).

ASCT-1124 (IL-6 Antagonist): Optimized for topical / transdermal delivery, enabling biologic-level potency for keloid / hypertrophic scars and other inflammatory skin diseases without systemic toxicity.

ASCT-83 (CTDSP1:REST Antagonist)

CTDSP1: C-terminal domain small phosphatase 1; REST: RE1 silencing transcription factor

ASCT-83 is a clinical stage first-in-class drug that antagonizes CTDSP1 and REST, which repress neuronal genes1. Prior to ASCT-83, CTDSP1 and REST were considered undruggable because they lack adequate binding pockets for small molecules and are localized in the nucleus, making them inaccessible to antibodies. CTDSP1 and REST are absent or only express at low levels in neurons and pancreatic beta cells (functionally similar to neurons). However, sugary and processed foods, or nerve injury can result in excessive expression in these tissues. High expression levels cause dysglycemia, neuropathy, and in the case in traumatic nerve and brain injury, an incomplete recovery. Additionally, brain cancers, like glioblastoma, have high CTDSP1 and REST levels. The published literature and our data strongly support that antagonizing CTDSP1 and REST improves the outcome of metabolic disorders, nerve injury, and brain cancer2-7.

Important for safety, most REST targets are transcriptionally unresponsive, because the basal organization of chromatin does not permit the epigenetic “writing” of a new set of instructions. However, ASCT-83 mediated-interference of REST chromatin binding in injured or diseased cells permits the re-establishment of durable chromatin state, restoring normal gene expression, thereby addressing the underlying cause of metabolic and/or neurologic symptoms, with a low potential for side effects.

Alcamena has received a “may proceed” letter from the Food and Drug Administration (FDA) to conduct a single and multiple ascending dose study in health human subjects to assess the tolerability and pharmacokinetics of ASCT-83 following daily subcutaneous administration.

Scientific references:

  1. Nesti, E., Corson, G. M., McCleskey, M., Oyer, J. A. & Mandel, G. C-terminal domain small phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation. Proc Natl Acad Sci U S A 111, E3929-3936 (2014). https://doi.org/10.1073/pnas.1414770111 [pii]10.1073/pnas.1414770111
  2. Uchida, H., Ma, L. & Ueda, H. Epigenetic Gene Silencing Underlies C-Fiber Dysfunctions in Neuropathic Pain. Journal of Neuroscience 30, 4806-4814 (2010). https://doi.org/10.1523/JNEUROSCI.5541-09.2010
  3. Zhang, F. et al. Repressor element 1-silencing transcription factor drives the development of chronic pain states. Pain (2019). https://doi.org/10.1097/j.pain.0000000000001633
  4. Zhang, J., Chen, S. R., Chen, H. & Pan, H. L. RE1-silencing transcription factor controls the acute-to-chronic neuropathic pain transition and Chrm2 receptor gene expression in primary sensory neurons. J Biol Chem 293, 19078-19091 (2018). https://doi.org/10.1074/jbc.RA118.005846
  5. Ueda, H. et al. A mimetic of the mSin3-binding helix of NRSF/REST ameliorates abnormal pain behavior in chronic pain models. Bioorg Med Chem Lett 27, 4705-4709 (2017). https://doi.org/10.1016/j.bmcl.2017.09.006
  6. Conti, L. et al. REST controls self-renewal and tumorigenic competence of human glioblastoma cells. PLoS One 7, e38486 (2012). https://doi.org/10.1371/journal.pone.0038486
  7. Zhang, Y. et al. Comprehensive Analysis of REST/NRSF Gene in Glioma and Its ceRNA Network Identification. Front Med (Lausanne) 8, 739624 (2021). https://doi.org/10.3389/fmed.2021.739624
  8. Martin, D. & Grapin-Botton, A. The Importance of REST for Development and Function of Beta Cells. Front Cell Dev Biol 5, 12 (2017). https://doi.org/10.3389/fcell.2017.00012

ASCT-83 for Obesity & Early T2D​

We target the CTDSP1:REST pathway to unlock the body’s production of BDNF, a potent natural appetite suppressant9, 10.

Obesity & Early T2D​

Appetite Suppressant / Weight loss​
Up to 3x BDNF
28% appetite
9% weight
BDNF 72 h / appetite & weight 1-month​
Model: BDNF human mesenchymal stem cells / appetite & weight in GLP dog study (daily SC administration at human relevant doses) ​

Scientific references:

  1. Xu, B. et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 6, 736-742 (2003). https://doi.org/10.1038/nn1073
  2. Zuccato, C. et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet 35, 76-83 (2003). https://doi.org/10.1038/ng1219​

Treating the Root Cause of Nerve Injury​

Current treatments fail to address the underlying injury-induced repression of neuronal genes by the CTDSP1:REST pathway11-14. ASCT-83 is designed to reverse this repression.​

Neuropathic Pain​

Rapid Pain Reduction​
Up to 70%
In just 1 Week​
Model: Rat spared nerve injury (mechanical & thermal pain)​

Peripheral Nerve Injury​

Motor Function Recovery​
Full Recovery​
In 4 Weeks​
Model: Rat sciatic nerve transection (restored from 40% deficit) ​

Scientific references:

  1. Uchida, H., Ma, L. & Ueda, H. Epigenetic Gene Silencing Underlies C-Fiber Dysfunctions in Neuropathic Pain. Journal of Neuroscience 30, 4806-4814 (2010). https://doi.org/10.1523/JNEUROSCI.5541-09.2010​
  2. Ueda, H. et al. A mimetic of the mSin3-binding helix of NRSF/REST ameliorates abnormal pain behavior in chronic pain models. Bioorg Med Chem Lett 27, 4705-4709 (2017). https://doi.org/10.1016/j.bmcl.2017.09.006​
  3. Zhang, J., Chen, S. R., Chen, H. & Pan, H. L. RE1-silencing transcription factor controls the acute-to-chronic neuropathic pain transition and Chrm2 receptor gene expression in primary sensory neurons. J Biol Chem 293, 19078-19091 (2018). https://doi.org/10.1074/jbc.RA118.005846​
  4. Xiao-Die, X. et al. Increased NRSF/REST in anterior cingulate cortex contributes to diabetes-related neuropathic pain. Biochem Biophys Res Commun 527, 785-790 (2020). https://doi.org/10.1016/j.bbrc.2020.04.106

ASCT-83 for Ischemic Stroke and Traumatic Brain injury (TBI)​

Blocking REST after injury is neuroprotective, prevents brain death, and improves cognitive function​15-19.

Ischemic Stroke & TBI​

60% less brain death
2x anxiety
2x cognitive function​
Brain death at 24 h; anxiety and cognitive function after two weeks of daily treatment at clinically relevant doses followed by a two-week dose free period.​
Model: ​ Brain death assessed in cultured hippocampi glutamate excitotoxicity assay; ​
 anxiety and cognitive function assessed in a controlled cortical impact rat TBI study​

Scientific references:

  1. Noh, K. M. et al. Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death. Proc Natl Acad Sci U S A 109, E962-971 (2012). https://doi.org/1121568109 [pii]10.1073/pnas.1121568109​
  2. Calderone, A. et al. Ischemic insults derepress the gene silencer REST in neurons destined to die. J Neurosci 23, 2112-2121 (2003). https://doi.org/23/6/2112 [pii]​
  3. Morris-Blanco, K. C. et al. Inhibition of the Epigenetic Regulator REST Ameliorates Ischemic Brain Injury. Mol Neurobiol 56, 2542-2550 (2019). https://doi.org/10.1007/s12035-018-1254-y​
  4. Cheng, Y. et al. Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration in mice. Nat Commun 13, 4418 (2022). https://doi.org/10.1038/s41467-022-31960-7​
  5. Liang, H. M. et al. By up-regulating mu- and delta-opioid receptors, neuron-restrictive silencer factor knockdown promotes neurological recovery after ischemia. Oncotarget 8, 101012-101025 (2017). https://doi.org/10.18632/oncotarget.18195

ASCT-83 for Huntington’s Disease​

ASCT-83 reverses the repression of neuronal genes by blocking REST, allowing them to express normally in Huntington’s disease20.
ASCT-83 eliminates nuclear REST​
48 hours post dose​
Model: HEK293 cells administered 500 to 1000 nM of ASCT-83 ​

Scientific references:

  1. Zuccato, C. et al. Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington’s disease. J Neurosci 27, 6972-6983 (2007). https://doi.org/10.1523/JNEUROSCI.4278-06.2007

ASCT-83 for Brain Cancer ​

In brain cancers REST acts as an oncogene by driving cancer progression1. Blocking REST induces cancer cell death and prevents cancer proliferation and migration21.
ASCT-83 kills glioblastoma cells (GBM)
ASCT-83 alone: 85% GBM cell death
ASCT-83 + Temozolomide (TMZ): 100% GBM cell death
ASCT-83 + TMZ: 75% TMZ resistant GBM cell death
Over 4 to 7 weeks​
Model: GBM U87 and GBM temozolomide resistant U251 cells using clinically relevant doses​

Scientific references:

  1. Kamal, M. M. et al. REST regulates oncogenic properties of glioblastoma stem cells. Stem Cells 30, 405-414 (2012). https://doi.org/10.1002/stem.1020
  2. Conti, L. et al. REST controls self-renewal and tumorigenic competence of human glioblastoma cells. PLoS One 7, e38486 (2012). https://doi.org/10.1371/journal.pone.0038486

ASCT-1 (Permeability Enhancer)

ASCT-1 (Permeability Enhancer)

Mechanism: ASCT-1 is engineered to optimize the delivery of small molecules, peptides, antibodies and oligonucleotides.

With high membrane affinity and efficient membrane permeability, it acts as a “molecular doorman”,  facilitating transmembrane passage and improving systemic uptake.

ASCT-1 is designed to improve drug cell and nuclear permeability and overall bioavailability.​

ASCT-1 enhanced antagonist (ASCT-456) efficacy against its nuclear-localized target REST: ​

Increased ASCT-456 REST antagonist activity from 64% to 100%

Increases ASCT-456-induced U87 GBM cell death from 63% to 100%.

Increases ASCT-456-induced U251-TMZ resistant GBM cell death from 0 to 76%

ASCT-1 exhibits no off-target effect on its own.​

48 hours post dose​
Model: HEK293, U87, and U256 cells using clinically relevant doses. ​

ASCT-1124 (IL-6 Antagonist)

Mechanism: A first-in-class topical peptide that binds directly to IL-6, blocking proliferation and inflammation signals. This offers a localized treatment, minimizing systemic side effects.​

ASCT-1124: Reduction and Prevention of Keloid / Hypertrophic Scars ​

ASCT-1124 is a topical peptide that delivers biologic-level potency directly only to the disease site, avoiding systemic toxicity.​

ASCT-1124 dose-dependently decreases proliferation of skin cells (keratinocytes) from 140% with IL-6 alone to zero in the presence of ASCT-1124.

40% reduction in skin thickness, 60% reduction in serum IL-6, and 75% reduction in serum IFN-γ in a humanized IMQ mouse model.​

Keratinocytes 12 hours post dose; humanized mice every 12 hours for 7 days.​
Model: Keratinocytes and imiquimod (IMQ)-induced humanize mouse model using clinically relevant doses. ​

ASCT-1201 (TNF-α Antagonist)

Pathophysiology: In both rheumatoid arthritis (RA) and psoriatic arthritis (PsA), elevated TNF-α in the synovial fluid and tissue causes joint destruction.

ASCT-1201: Refractory Monoarthritis, RA and PsA​

ASCT-1201 is a once-monthly intra-articular (IA) injection that treats only the inflamed joint, eliminating systemic immunosuppression.​

Low nanomolar affinity with no off-target activity.

>40% Reduction in TNF-α signaling in a reporter assay, confirming potent target engagement.​

12 hours post dose​

Model: TNF reporter strain